Diane Eardley | University of California (original) (raw)

Papers by Diane Eardley

Research paper thumbnail of Modulation of Help and Suppression in a Hapten-Carrier System

The Journal of Immunology, Mar 1, 1976

Research paper thumbnail of Characterization of a monoclonal rat anti-mouse interleukin 2 (IL-2) receptor antibody and its use in the biochemical characterization of the murine IL-2 receptor

Clinical immunology and immunopathology, 1985

Anti-murine interleukin 2 (IL-2) receptor monoclonal antibodies (mAb) were made from rats immuniz... more Anti-murine interleukin 2 (IL-2) receptor monoclonal antibodies (mAb) were made from rats immunized with murine cytotoxic lymphocytes. One mAb, designated M7/20, strongly inhibited the proliferation of both IL-2 dependent CTLL-2 cells and concanavalin A (Con A)-induced T-cell blasts. Inhibition was linearly dependent on the concentrations of both M7/20 and IL-2. Utilizing FACS analysis, M7/20 was shown to bind selectively to mitogen-activated T lymphocytes and, to a lesser degree, to activated B lymphocytes. 125I-Labeled M7/20 binding assays indicated that 48-hr Con A-induced T-cell blasts possessed 89,000 binding sites/cell with a Kd of 1.2 X 10(-9) M. Competitive binding analyses indicated that M7/20 and IL-2 occupy the same or overlapping cell surface sites. Preliminary biochemical characterization of M7/20 immunoprecipitates of detergent extracts from both surface-iodinated and internally D-[3H]glucosamine-labeled T lymphoblasts indicated that the murine IL-2 receptor is an N-gl...

Research paper thumbnail of Monoclonal Antibodies Specific for Sulfated Polysaccharides on the Surface of Macrocystis Pyrifera (Phaeophyceae) 1

... The antibod-ies gave roughly similar patterns of labeling by im-Table 1. Reactivity oj MacTwy... more ... The antibod-ies gave roughly similar patterns of labeling by im-Table 1. Reactivity oj MacTwystis-gmrmtetl monoclonal antibodies and anti-tubulin antibody to gametophytes of Macrocystis py ri fera anil Pterygophora californica. ... Page 7. 60 DI Л NF. I). KAKI >l.FY FT AL. ...

Research paper thumbnail of Book Review:The Reticuloendothelial System: A Comprehensive Treatise. Volume 6: Immunology. Herman Friedman, Mario Escobar, Sherwood M. Richard, Joseph A. Bellanti, Herbert B. Herscowitz

Quarterly Review of Biology, 1985

Research paper thumbnail of T cells in a suppressor circuit and non-T: non-B cells bear different 1-J determinants

Immunogenetics, 1981

T cells involved in the generation of suppressor activity bear an I-J-subregion controlled determ... more T cells involved in the generation of suppressor activity bear an I-J-subregion controlled determinant (e. g., J1) which is distinct from that (e. g., J1) found on non-T: non-13 accessory cells. T-cell subsets examined include Ly-1 inducer and Ly-1,2 acceptor cells which collaborate to generate suppressor activity in the in vitro sheep red blood cell antibody system. Non-T:non-B accessory cells examined include accessory cells involved in concanavalin-A induced, T-cell proliferative responses and in in vitro antibody responses to sheep red blood cells. These results provide evidence for serologic and genetic complexity of the I-J subregion of the murine H-2 gene complex.

Research paper thumbnail of Immunoregulatory circuits which modulate responsiveness to suppressor cell signals: characterization of an effector cell in the contrasuppressor circuit

European Journal of Immunology, 1981

Spleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the abilit... more Spleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the ability to block the activity of suppressor T cells, a phenomenon that is referred to as contrasuppression. The effector cell which is derived from the interactions among the cells which comprise a contrasuppressor “circuit” is an Ly-1 T cell. It can be separated from Ly-1 helper cells by three criteria other than function: its generation is dependent on Ly-2+ cells, it is I-J+, and it sticks to the Vicia villosa lectin. Those cells which deliver help to B cells under the experimental conditions studied are not dependent on Ly-2+ cells for generation and neither express determinants that our anti-I-J antisera recognize nor stick to V. villosa.The mechanism by which these Ly-1 contrasuppressor cells function was elucidated by adding them to “intermediate cultures” containing activated Ly-2 suppressor cells and in vivo immunized Ly-1.1-congenic helper cells. After 48 h in these intermediate cultures, the neonatal Ly-1.2 contrasuppressor cells and the Ly-2 suppressor cells were removed by treatment with the appropriate antiserum plus complement. The remaining activity of the in vivo generated Ly-1.1 helper cells was assayed in fresh cultures of B cells. The contrasuppressor cells not only diminished suppression of the Ly-1 helper cells by the Ly-2 suppressor cells in the intermediate culture, but actually conferred a state of relative resistance to suppression upon the helper cells. This state persisted after the contrasuppressor cells were removed. Why such a cellular circuit, which confers resistance to suppression, might be beneficial to neonatal mice and how considering its attributes might help explain some immunological paradoxes is the subject of discussion.

Research paper thumbnail of Immunoregulatory circuits among t-cell sets. I. T-helper cells induce other t-cell sets to exert feedback inhibition

Journal of Experimental Medicine, 1978

The T-lymphocyte population is divisible into several subclasses; each subclass possesses a disti... more The T-lymphocyte population is divisible into several subclasses; each subclass possesses a distinctive genetic program which combines information for cell-surface phenotype and function (1). In the mouse, there is evidence that T cells which express the Thyl+Lyl+Ly23 -surface phenotype CLyl cells") are programmed for helper (TH) 1 function. In contrast, T cells that express the Thyl+Lyl-Ly23 ÷ surface phenotype CLy23 cells") are programmed for suppressor (Ts) function (1). Isolation of these two T-cell subclasses in mice depleted of T cells CB mice") has indicated that each belongs to an independent line or branch of thymus-dependent differentiation (2). A third major T-cell subclass, expressing the surface phenotype Lyl+2+3 +, can react to antigen and differentiate to Ly23 + cytotoxic effector cells , suggesting that this subclass probably contains precursor cells that have acquired receptors for antigen but have not yet become committed to either TH or Tc~s function (3).

Research paper thumbnail of Association of defective feedback suppressor t cell activity with autoimmunity in nzb mice

Arthritis and Rheumatism, 1978

A “feedback suppressor T cell” highly dependent on signals from Ly 1 T helper cells for activatio... more A “feedback suppressor T cell” highly dependent on signals from Ly 1 T helper cells for activation is described. The signal from the Ly 1 cell binds to Fc-like receptors on macrophage membranes. The feedback suppressor cell expresses all three Ly antigens as well as the Qa 1 antigen on its surface, is very sensitive to low doses of cyclophosphamide, disappears relatively rapidly after adult thymectomy, and cannot be demonstrated in NZB mice 6 weeks or older.

Research paper thumbnail of Definition of Two Pathways for Generation of Suppressor T-Cell Activity

Proceedings of The National Academy of Sciences, 1983

Antigen-stimulated Ly1 cells induce T cells from nonimmune donors to develop potent feedback supp... more Antigen-stimulated Ly1 cells induce T cells from nonimmune donors to develop potent feedback suppressive activity. Suppression is mediated by Ly23 suppressor T (Ts) cells, which are generated from either Ly23 or Ly123 precursors. Ts activity generated from Ly23 precursors requires a strong inducer signal and is rapidly expressed but short lived. In contrast, Ts activity from Ly123 precursors is relatively long lived and is efficiently generated by relatively low levels of inducer signals. Induction of both Ly123 and Ly23 precursors to become Ts cells requires that both cells share genes linked to the Ig-H locus.

Research paper thumbnail of CIRCUITS THAT MODULATE RESPONSIVENESS TO SUPPRESSOR CELL SIGNALS Failure of B10 Mice to Respond to Suppressor Factors Can Be Overcome by Quenching the Contrasuppressor Circuit

Research paper thumbnail of Isolation and partial characterization of antigen-binding molecules produced by In vitro ‘educated’ T cells

Molecular Immunology, 1980

Paenibacillus sp. strain B2, isolated from the mycorrhizosphere of sorghum colonized by Glomus mo... more Paenibacillus sp. strain B2, isolated from the mycorrhizosphere of sorghum colonized by Glomus mosseae, produces an antagonistic factor. This factor has a broad spectrum of activity against gram-positive and gram-negative bacteria and also against fungi. The antagonistic factor was isolated from the bacterial culture medium and purified by cation-exchange, reverse-phase, and size exclusion chromatography. The purified factor could be separated into three active compounds following characterization by amino acid analysis and by combined reverse-phase chromatography and mass spectrometry (liquid chromatography-mass spectrometry and mass spectrometry-mass spectrometry). The first compound had the same retention time as polymyxin B 1 , whereas the two other compounds were more hydrophobic. The molecular masses of the latter compounds are 1,184.7 and 1,202.7 Da, respectively, and their structure is similar to that of polymyxin B 1 , with a cyclic heptapeptide moiety attached to a tripeptide side chain and a fatty acyl residue. They both contain threonine, phenylalanine, leucine, and 2,4-diaminobutyric acid residues. The peptide with a molecular mass of 1,184.7 contains a 2,3-didehydrobutyrine residue with a molecular mass of 101 Da replacing a threonine at the A2 position of the polymyxin side chain. This modification could explain the broader range of antagonistic activity of this peptide compared to that of polymyxin B.

Research paper thumbnail of Genetic control of immunoregulatory circuits. Genes linked to the ig locus govern communication between regulatory t-cell sets

Journal of Experimental Medicine, 1979

Research paper thumbnail of Functional inactivation of suppressor T cells by heat-killed macrophages

Research paper thumbnail of Suppressor cells. Dependence on assay conditions for functional activity

Journal of Experimental Medicine, 1976

Research paper thumbnail of Immunoregulatory circuits among t-cells sets. Identification of a subpopulation of t-helper cells that induces feedback inhibition

Journal of Experimental Medicine, 1978

Antigen-stimulated Lyl cells induce B cells to secrete antibody and induce a nonimmune set of T c... more Antigen-stimulated Lyl cells induce B cells to secrete antibody and induce a nonimmune set of T cells (surface phenotype Ly123+Qal +) to participate in specific suppressor activity (1, 2). We have referred to this suppressive T-T interaction as feedback inhibition because (a) the level of suppression exerted by a fixed number of nonimmune T cells increase in direct proportion to the numbers of antigen-stimulated Lyl cells (0.5-5 × 105) in cell culture and (b) one consequence of Ly123-assoeiated suppression is a reduction in the delivery of T-helper activity to B cells.

Research paper thumbnail of Ly1 inducer and Ly1,2 acceptor t cells in the feedback suppression circuit bear an I-J-subregion controlled determinant

Immunogenetics, 1980

An I-J-subregion controlled determinant is expressed on Ly-1 inducer and Ly-1,2 acceptor T cells ... more An I-J-subregion controlled determinant is expressed on Ly-1 inducer and Ly-1,2 acceptor T cells in the feedback suppression circuit. Ly-1 T cells absorb the I-J antibody reactive with the Ly-1,2 acceptor T cell, suggesting that both inducer and acceptor T cells have the same 1-J determinant. Since less than 10 percent of Ly-1 or Ly-1,2 T cells are killed by anti-I-J plus complement treatment, the I-J determinant demarcates functionally distinct subsets of both the Ly-1 and Ly-1,2 T-cell sets. This I-J determinant is not expressed on a detectable number of Ly-1 helper T cells which induce B lymphocytes to produce anti-sheep red cell antibody in tissue culture.

Research paper thumbnail of Feedback induction of suppressor t-cell activity

Journal of Experimental Medicine, 1975

Adoptively transferred carrier immune T cells interact with nonimmune T cells in recipients in a ... more Adoptively transferred carrier immune T cells interact with nonimmune T cells in recipients in a fashion which generates specific immunosuppression although both the immune and normal cells function quite well as helper cells when not admixed.

Research paper thumbnail of T cells in a suppressor circuit and non-T: non-B cells bear different 1-J determinants

Immunogenetics, 1981

T cells involved in the generation of suppressor activity bear an I-J-subregion controlled determ... more T cells involved in the generation of suppressor activity bear an I-J-subregion controlled determinant (e. g., J1) which is distinct from that (e. g., J1) found on non-T: non-13 accessory cells. T-cell subsets examined include Ly-1 inducer and Ly-1,2 acceptor cells which collaborate to generate suppressor activity in the in vitro sheep red blood cell antibody system. Non-T:non-B accessory cells examined include accessory cells involved in concanavalin-A induced, T-cell proliferative responses and in in vitro antibody responses to sheep red blood cells. These results provide evidence for serologic and genetic complexity of the I-J subregion of the murine H-2 gene complex.

Research paper thumbnail of Immunoregulatory circuits which modulate responsiveness to suppressor cell signals: characterization of an effector cell in the contrasuppressor circuit

European Journal of Immunology, 1981

Spleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the abilit... more Spleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the ability to block the activity of suppressor T cells, a phenomenon that is referred to as contrasuppression. The effector cell which is derived from the interactions among the cells which comprise a contrasuppressor “circuit” is an Ly-1 T cell. It can be separated from Ly-1 helper cells by three criteria other than function: its generation is dependent on Ly-2+ cells, it is I-J+, and it sticks to the Vicia villosa lectin. Those cells which deliver help to B cells under the experimental conditions studied are not dependent on Ly-2+ cells for generation and neither express determinants that our anti-I-J antisera recognize nor stick to V. villosa.The mechanism by which these Ly-1 contrasuppressor cells function was elucidated by adding them to “intermediate cultures” containing activated Ly-2 suppressor cells and in vivo immunized Ly-1.1-congenic helper cells. After 48 h in these intermediate cultures, the neonatal Ly-1.2 contrasuppressor cells and the Ly-2 suppressor cells were removed by treatment with the appropriate antiserum plus complement. The remaining activity of the in vivo generated Ly-1.1 helper cells was assayed in fresh cultures of B cells. The contrasuppressor cells not only diminished suppression of the Ly-1 helper cells by the Ly-2 suppressor cells in the intermediate culture, but actually conferred a state of relative resistance to suppression upon the helper cells. This state persisted after the contrasuppressor cells were removed. Why such a cellular circuit, which confers resistance to suppression, might be beneficial to neonatal mice and how considering its attributes might help explain some immunological paradoxes is the subject of discussion.

Research paper thumbnail of Immunoregulatory circuits among t-cell sets. I. T-helper cells induce other t-cell sets to exert feedback inhibition

Journal of Experimental Medicine, 1978

The T-lymphocyte population is divisible into several subclasses; each subclass possesses a disti... more The T-lymphocyte population is divisible into several subclasses; each subclass possesses a distinctive genetic program which combines information for cell-surface phenotype and function (1). In the mouse, there is evidence that T cells which express the Thyl+Lyl+Ly23 -surface phenotype CLyl cells") are programmed for helper (TH) 1 function. In contrast, T cells that express the Thyl+Lyl-Ly23 ÷ surface phenotype CLy23 cells") are programmed for suppressor (Ts) function (1). Isolation of these two T-cell subclasses in mice depleted of T cells CB mice") has indicated that each belongs to an independent line or branch of thymus-dependent differentiation (2). A third major T-cell subclass, expressing the surface phenotype Lyl+2+3 +, can react to antigen and differentiate to Ly23 + cytotoxic effector cells , suggesting that this subclass probably contains precursor cells that have acquired receptors for antigen but have not yet become committed to either TH or Tc~s function (3).

Research paper thumbnail of Modulation of Help and Suppression in a Hapten-Carrier System

The Journal of Immunology, Mar 1, 1976

Research paper thumbnail of Characterization of a monoclonal rat anti-mouse interleukin 2 (IL-2) receptor antibody and its use in the biochemical characterization of the murine IL-2 receptor

Clinical immunology and immunopathology, 1985

Anti-murine interleukin 2 (IL-2) receptor monoclonal antibodies (mAb) were made from rats immuniz... more Anti-murine interleukin 2 (IL-2) receptor monoclonal antibodies (mAb) were made from rats immunized with murine cytotoxic lymphocytes. One mAb, designated M7/20, strongly inhibited the proliferation of both IL-2 dependent CTLL-2 cells and concanavalin A (Con A)-induced T-cell blasts. Inhibition was linearly dependent on the concentrations of both M7/20 and IL-2. Utilizing FACS analysis, M7/20 was shown to bind selectively to mitogen-activated T lymphocytes and, to a lesser degree, to activated B lymphocytes. 125I-Labeled M7/20 binding assays indicated that 48-hr Con A-induced T-cell blasts possessed 89,000 binding sites/cell with a Kd of 1.2 X 10(-9) M. Competitive binding analyses indicated that M7/20 and IL-2 occupy the same or overlapping cell surface sites. Preliminary biochemical characterization of M7/20 immunoprecipitates of detergent extracts from both surface-iodinated and internally D-[3H]glucosamine-labeled T lymphoblasts indicated that the murine IL-2 receptor is an N-gl...

Research paper thumbnail of Monoclonal Antibodies Specific for Sulfated Polysaccharides on the Surface of Macrocystis Pyrifera (Phaeophyceae) 1

... The antibod-ies gave roughly similar patterns of labeling by im-Table 1. Reactivity oj MacTwy... more ... The antibod-ies gave roughly similar patterns of labeling by im-Table 1. Reactivity oj MacTwystis-gmrmtetl monoclonal antibodies and anti-tubulin antibody to gametophytes of Macrocystis py ri fera anil Pterygophora californica. ... Page 7. 60 DI Л NF. I). KAKI >l.FY FT AL. ...

Research paper thumbnail of Book Review:The Reticuloendothelial System: A Comprehensive Treatise. Volume 6: Immunology. Herman Friedman, Mario Escobar, Sherwood M. Richard, Joseph A. Bellanti, Herbert B. Herscowitz

Quarterly Review of Biology, 1985

Research paper thumbnail of T cells in a suppressor circuit and non-T: non-B cells bear different 1-J determinants

Immunogenetics, 1981

T cells involved in the generation of suppressor activity bear an I-J-subregion controlled determ... more T cells involved in the generation of suppressor activity bear an I-J-subregion controlled determinant (e. g., J1) which is distinct from that (e. g., J1) found on non-T: non-13 accessory cells. T-cell subsets examined include Ly-1 inducer and Ly-1,2 acceptor cells which collaborate to generate suppressor activity in the in vitro sheep red blood cell antibody system. Non-T:non-B accessory cells examined include accessory cells involved in concanavalin-A induced, T-cell proliferative responses and in in vitro antibody responses to sheep red blood cells. These results provide evidence for serologic and genetic complexity of the I-J subregion of the murine H-2 gene complex.

Research paper thumbnail of Immunoregulatory circuits which modulate responsiveness to suppressor cell signals: characterization of an effector cell in the contrasuppressor circuit

European Journal of Immunology, 1981

Spleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the abilit... more Spleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the ability to block the activity of suppressor T cells, a phenomenon that is referred to as contrasuppression. The effector cell which is derived from the interactions among the cells which comprise a contrasuppressor “circuit” is an Ly-1 T cell. It can be separated from Ly-1 helper cells by three criteria other than function: its generation is dependent on Ly-2+ cells, it is I-J+, and it sticks to the Vicia villosa lectin. Those cells which deliver help to B cells under the experimental conditions studied are not dependent on Ly-2+ cells for generation and neither express determinants that our anti-I-J antisera recognize nor stick to V. villosa.The mechanism by which these Ly-1 contrasuppressor cells function was elucidated by adding them to “intermediate cultures” containing activated Ly-2 suppressor cells and in vivo immunized Ly-1.1-congenic helper cells. After 48 h in these intermediate cultures, the neonatal Ly-1.2 contrasuppressor cells and the Ly-2 suppressor cells were removed by treatment with the appropriate antiserum plus complement. The remaining activity of the in vivo generated Ly-1.1 helper cells was assayed in fresh cultures of B cells. The contrasuppressor cells not only diminished suppression of the Ly-1 helper cells by the Ly-2 suppressor cells in the intermediate culture, but actually conferred a state of relative resistance to suppression upon the helper cells. This state persisted after the contrasuppressor cells were removed. Why such a cellular circuit, which confers resistance to suppression, might be beneficial to neonatal mice and how considering its attributes might help explain some immunological paradoxes is the subject of discussion.

Research paper thumbnail of Immunoregulatory circuits among t-cell sets. I. T-helper cells induce other t-cell sets to exert feedback inhibition

Journal of Experimental Medicine, 1978

The T-lymphocyte population is divisible into several subclasses; each subclass possesses a disti... more The T-lymphocyte population is divisible into several subclasses; each subclass possesses a distinctive genetic program which combines information for cell-surface phenotype and function (1). In the mouse, there is evidence that T cells which express the Thyl+Lyl+Ly23 -surface phenotype CLyl cells") are programmed for helper (TH) 1 function. In contrast, T cells that express the Thyl+Lyl-Ly23 ÷ surface phenotype CLy23 cells") are programmed for suppressor (Ts) function (1). Isolation of these two T-cell subclasses in mice depleted of T cells CB mice") has indicated that each belongs to an independent line or branch of thymus-dependent differentiation (2). A third major T-cell subclass, expressing the surface phenotype Lyl+2+3 +, can react to antigen and differentiate to Ly23 + cytotoxic effector cells , suggesting that this subclass probably contains precursor cells that have acquired receptors for antigen but have not yet become committed to either TH or Tc~s function (3).

Research paper thumbnail of Association of defective feedback suppressor t cell activity with autoimmunity in nzb mice

Arthritis and Rheumatism, 1978

A “feedback suppressor T cell” highly dependent on signals from Ly 1 T helper cells for activatio... more A “feedback suppressor T cell” highly dependent on signals from Ly 1 T helper cells for activation is described. The signal from the Ly 1 cell binds to Fc-like receptors on macrophage membranes. The feedback suppressor cell expresses all three Ly antigens as well as the Qa 1 antigen on its surface, is very sensitive to low doses of cyclophosphamide, disappears relatively rapidly after adult thymectomy, and cannot be demonstrated in NZB mice 6 weeks or older.

Research paper thumbnail of Definition of Two Pathways for Generation of Suppressor T-Cell Activity

Proceedings of The National Academy of Sciences, 1983

Antigen-stimulated Ly1 cells induce T cells from nonimmune donors to develop potent feedback supp... more Antigen-stimulated Ly1 cells induce T cells from nonimmune donors to develop potent feedback suppressive activity. Suppression is mediated by Ly23 suppressor T (Ts) cells, which are generated from either Ly23 or Ly123 precursors. Ts activity generated from Ly23 precursors requires a strong inducer signal and is rapidly expressed but short lived. In contrast, Ts activity from Ly123 precursors is relatively long lived and is efficiently generated by relatively low levels of inducer signals. Induction of both Ly123 and Ly23 precursors to become Ts cells requires that both cells share genes linked to the Ig-H locus.

Research paper thumbnail of CIRCUITS THAT MODULATE RESPONSIVENESS TO SUPPRESSOR CELL SIGNALS Failure of B10 Mice to Respond to Suppressor Factors Can Be Overcome by Quenching the Contrasuppressor Circuit

Research paper thumbnail of Isolation and partial characterization of antigen-binding molecules produced by In vitro ‘educated’ T cells

Molecular Immunology, 1980

Paenibacillus sp. strain B2, isolated from the mycorrhizosphere of sorghum colonized by Glomus mo... more Paenibacillus sp. strain B2, isolated from the mycorrhizosphere of sorghum colonized by Glomus mosseae, produces an antagonistic factor. This factor has a broad spectrum of activity against gram-positive and gram-negative bacteria and also against fungi. The antagonistic factor was isolated from the bacterial culture medium and purified by cation-exchange, reverse-phase, and size exclusion chromatography. The purified factor could be separated into three active compounds following characterization by amino acid analysis and by combined reverse-phase chromatography and mass spectrometry (liquid chromatography-mass spectrometry and mass spectrometry-mass spectrometry). The first compound had the same retention time as polymyxin B 1 , whereas the two other compounds were more hydrophobic. The molecular masses of the latter compounds are 1,184.7 and 1,202.7 Da, respectively, and their structure is similar to that of polymyxin B 1 , with a cyclic heptapeptide moiety attached to a tripeptide side chain and a fatty acyl residue. They both contain threonine, phenylalanine, leucine, and 2,4-diaminobutyric acid residues. The peptide with a molecular mass of 1,184.7 contains a 2,3-didehydrobutyrine residue with a molecular mass of 101 Da replacing a threonine at the A2 position of the polymyxin side chain. This modification could explain the broader range of antagonistic activity of this peptide compared to that of polymyxin B.

Research paper thumbnail of Genetic control of immunoregulatory circuits. Genes linked to the ig locus govern communication between regulatory t-cell sets

Journal of Experimental Medicine, 1979

Research paper thumbnail of Functional inactivation of suppressor T cells by heat-killed macrophages

Research paper thumbnail of Suppressor cells. Dependence on assay conditions for functional activity

Journal of Experimental Medicine, 1976

Research paper thumbnail of Immunoregulatory circuits among t-cells sets. Identification of a subpopulation of t-helper cells that induces feedback inhibition

Journal of Experimental Medicine, 1978

Antigen-stimulated Lyl cells induce B cells to secrete antibody and induce a nonimmune set of T c... more Antigen-stimulated Lyl cells induce B cells to secrete antibody and induce a nonimmune set of T cells (surface phenotype Ly123+Qal +) to participate in specific suppressor activity (1, 2). We have referred to this suppressive T-T interaction as feedback inhibition because (a) the level of suppression exerted by a fixed number of nonimmune T cells increase in direct proportion to the numbers of antigen-stimulated Lyl cells (0.5-5 × 105) in cell culture and (b) one consequence of Ly123-assoeiated suppression is a reduction in the delivery of T-helper activity to B cells.

Research paper thumbnail of Ly1 inducer and Ly1,2 acceptor t cells in the feedback suppression circuit bear an I-J-subregion controlled determinant

Immunogenetics, 1980

An I-J-subregion controlled determinant is expressed on Ly-1 inducer and Ly-1,2 acceptor T cells ... more An I-J-subregion controlled determinant is expressed on Ly-1 inducer and Ly-1,2 acceptor T cells in the feedback suppression circuit. Ly-1 T cells absorb the I-J antibody reactive with the Ly-1,2 acceptor T cell, suggesting that both inducer and acceptor T cells have the same 1-J determinant. Since less than 10 percent of Ly-1 or Ly-1,2 T cells are killed by anti-I-J plus complement treatment, the I-J determinant demarcates functionally distinct subsets of both the Ly-1 and Ly-1,2 T-cell sets. This I-J determinant is not expressed on a detectable number of Ly-1 helper T cells which induce B lymphocytes to produce anti-sheep red cell antibody in tissue culture.

Research paper thumbnail of Feedback induction of suppressor t-cell activity

Journal of Experimental Medicine, 1975

Adoptively transferred carrier immune T cells interact with nonimmune T cells in recipients in a ... more Adoptively transferred carrier immune T cells interact with nonimmune T cells in recipients in a fashion which generates specific immunosuppression although both the immune and normal cells function quite well as helper cells when not admixed.

Research paper thumbnail of T cells in a suppressor circuit and non-T: non-B cells bear different 1-J determinants

Immunogenetics, 1981

T cells involved in the generation of suppressor activity bear an I-J-subregion controlled determ... more T cells involved in the generation of suppressor activity bear an I-J-subregion controlled determinant (e. g., J1) which is distinct from that (e. g., J1) found on non-T: non-13 accessory cells. T-cell subsets examined include Ly-1 inducer and Ly-1,2 acceptor cells which collaborate to generate suppressor activity in the in vitro sheep red blood cell antibody system. Non-T:non-B accessory cells examined include accessory cells involved in concanavalin-A induced, T-cell proliferative responses and in in vitro antibody responses to sheep red blood cells. These results provide evidence for serologic and genetic complexity of the I-J subregion of the murine H-2 gene complex.

Research paper thumbnail of Immunoregulatory circuits which modulate responsiveness to suppressor cell signals: characterization of an effector cell in the contrasuppressor circuit

European Journal of Immunology, 1981

Spleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the abilit... more Spleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the ability to block the activity of suppressor T cells, a phenomenon that is referred to as contrasuppression. The effector cell which is derived from the interactions among the cells which comprise a contrasuppressor “circuit” is an Ly-1 T cell. It can be separated from Ly-1 helper cells by three criteria other than function: its generation is dependent on Ly-2+ cells, it is I-J+, and it sticks to the Vicia villosa lectin. Those cells which deliver help to B cells under the experimental conditions studied are not dependent on Ly-2+ cells for generation and neither express determinants that our anti-I-J antisera recognize nor stick to V. villosa.The mechanism by which these Ly-1 contrasuppressor cells function was elucidated by adding them to “intermediate cultures” containing activated Ly-2 suppressor cells and in vivo immunized Ly-1.1-congenic helper cells. After 48 h in these intermediate cultures, the neonatal Ly-1.2 contrasuppressor cells and the Ly-2 suppressor cells were removed by treatment with the appropriate antiserum plus complement. The remaining activity of the in vivo generated Ly-1.1 helper cells was assayed in fresh cultures of B cells. The contrasuppressor cells not only diminished suppression of the Ly-1 helper cells by the Ly-2 suppressor cells in the intermediate culture, but actually conferred a state of relative resistance to suppression upon the helper cells. This state persisted after the contrasuppressor cells were removed. Why such a cellular circuit, which confers resistance to suppression, might be beneficial to neonatal mice and how considering its attributes might help explain some immunological paradoxes is the subject of discussion.

Research paper thumbnail of Immunoregulatory circuits among t-cell sets. I. T-helper cells induce other t-cell sets to exert feedback inhibition

Journal of Experimental Medicine, 1978

The T-lymphocyte population is divisible into several subclasses; each subclass possesses a disti... more The T-lymphocyte population is divisible into several subclasses; each subclass possesses a distinctive genetic program which combines information for cell-surface phenotype and function (1). In the mouse, there is evidence that T cells which express the Thyl+Lyl+Ly23 -surface phenotype CLyl cells") are programmed for helper (TH) 1 function. In contrast, T cells that express the Thyl+Lyl-Ly23 ÷ surface phenotype CLy23 cells") are programmed for suppressor (Ts) function (1). Isolation of these two T-cell subclasses in mice depleted of T cells CB mice") has indicated that each belongs to an independent line or branch of thymus-dependent differentiation (2). A third major T-cell subclass, expressing the surface phenotype Lyl+2+3 +, can react to antigen and differentiate to Ly23 + cytotoxic effector cells , suggesting that this subclass probably contains precursor cells that have acquired receptors for antigen but have not yet become committed to either TH or Tc~s function (3).