Ramesh Kamat - Academia.edu (original) (raw)

Papers by Ramesh Kamat

Research paper thumbnail of Studies on T Cell Clonal Expansion

The Journal of Immunology

Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at variou... more Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at various stages of the immune response and cultured in vitro in the presence and absence of antigen. Killer T cell activity in immune spleens could not be demonstrated until 6 or 7 days after antigen, but spleen cells harvested as early as 3 or 4 days and cultured for 24 hr at 37°C showed significant cytotoxicity. This increased activity was not augmented further by culturing with antigen. “Memory” T cells, whose in vitro differentiation into killer cells required the presence of antigen, could not be demonstrated until 9 or 10 days after alloantigenic stimulation. Once produced, however, these cells persisted for at least 6 months. Memory cells, like killer T cells bound avidly to homologous allogeneic monolayers. There were indications that the memory T cell pool was heterogeneous. On one hand, when cells harvested 10 days after stimulation were exposed to antigen in vitro, their lytic activi...

Research paper thumbnail of Studies on T Cell Clonal Expansion

The Journal of Immunology

Adult C57BL/6 mice immunized i.p. with an allogeneic mastocytoma cell line (P815 of the DBA/2 str... more Adult C57BL/6 mice immunized i.p. with an allogeneic mastocytoma cell line (P815 of the DBA/2 strain) develop cytolytically active T cells. Activity peaks at 10 to 11 days and falls rapidly thereafter. We have observed an anomalous in vitro behavior of effector cell populations harvested during this decline. The lytic activity of spleen cells harvested 12 to 18 days after alloantigen was markedly augmented after culture for 24 hr at 37°C. The augmented lytic activity was caused by T cells and specificity exhibited was identical to the pre-culture population. No augmentation of lytic activity occurred when cells were cultured at 4°C or when they were treated with a protein synthetic inhibitor (pactamycin) at concentrations which did not compromise cytotoxic expression by the starting population. Augmentation of cytolysis was independent of DNA synthesis and did not require the presence of added antigen. When immune lymphoid cell populations were depleted of effector cells by adsorpti...

Research paper thumbnail of Immunomodulatory properties of porins of some members of the family Enterobacteriaceae

Infection and Immunity, 1997

The outer membrane protein (OMP) preparation of Salmonella typhi was observed to have several imm... more The outer membrane protein (OMP) preparation of Salmonella typhi was observed to have several immunomodulatory properties. Treatment of mice with an intraperitoneal injection of the OMP preparation enhanced both cellular and humoral responses of the mice to an unrelated antigen, a killed vaccine of Mycobacterium vaccae; both the delayed-type hypersensitivity (DTH) response and the antibody titers were enhanced. The predominant isotype of the antibody shifted from immunoglobulin G1 (IgG1) to IgG2a upon treatment with OMP. Treatment of mice with the OMP preparation improved the efficiency of in vitro antigen presentation by the peritoneal cells and also induced the cells to secrete interleukin-1. Treatment with the lipopolysaccharide (LPS) preparation of S. typhi had the opposite effect; i.e., the DTH response to M. vaccae was suppressed. Treatment with OMP neutralized the suppressive effects of LPS. The OMP preparation also had an enhancing effect on the innate immune mechanisms of t...

Research paper thumbnail of The Secretory Immunoglobulin A Response in the Gut

Biochemical Society Transactions, 1977

Humoral immunity manifest in the mammalian gut is often due to the presence there of sIgA (secret... more Humoral immunity manifest in the mammalian gut is often due to the presence there of sIgA (secretory immunoglobulin A) antibodies. A considerable proportion of antibodies of this immunoglobulin isotype are synthesized locally by plasma cells, which are abundant in intestinal lamina propria. B-lymphocyte precursors for IgAsecreting plasma cells ('IgA plasma cells') appear to derive from the Peyer's patches (aggregated lymphatic follicles) of the small intestine. The Peyer's patches of rabbits contain a subpopulation of B-lymphocytes that can repopulate the spleen and lamina propria of irradiated allogeneic recipients with IgA plasma cells (Craig & Cebra, 1971). Pokeweed mitogen stimulates this subpopulation in vitro to generate IgA plasma cells (Jones et al., 1974). The immediate precursors for IgA plasma cells have been isolated in the subpopulation of Peyer's-patch cells bearing membrane Fab, and lacking membrane IgM by fluorescence-activated cell-sorting (Jones et al., 1974; Jones & Cebra, 1974). In addition to supplying precursors for IgA plasma cells, an 'antigen-sampling' role has been ascribed to Peyer's patches (Bockman & Cooper, 1973). Whole protein molecules may pass intact across their specialized dome epithelial cells and arrive in the midst of B-lymphocyte follicles. Thus IgA precursors may have their first encounter with antigen in the Peyer's patches, be stimulated to divide, and migrate in lymph/blood to intestinal lamina propria and generate plasma cells. We have devised an adoptive transfer system to compare the antigen-sensitivity of Peyer's-patch cells with cells from peripheral lymph nodes and spleen (Cebra et al., 1977a,b). Syngeneic or congeneic (CB20+Balb/c) cells were transferred into sublethally irradiated (600rad) recipients which were then challenged 1 day later with 5 x lo8 sheep erythrocytes. Antibody-forming cells in the recipients' spleens were enumerated at various times thereafter by the Jerne plaque assay and by facilitating antisera to distinguish cells making IgM, IgGl, IgG2 and IgA isotopes. Fluorochrome-labelled alloantisera, which distinguished IgA from CB20 (Ig-2*) and Balb/c (Ig-2") congeneic mice, were used to determine the origin of IgA plasma cells in recipient mice. The Peyer's-patch cells were as effective in adoptively transferring IgM and IgG responses as cells from peripheral lymph nodes or spleen. However, only Peyer's-patch cells transferred a significant IgA response, which began at about day 10 after transfer and reached a maximum of IgA Vol. 5

Research paper thumbnail of The secretory IgA System of the Gut

Novartis Foundation Symposia, 2008

Most commonly, humoral immunity manifested in the gastrointestinal tract of mammals is due to the... more Most commonly, humoral immunity manifested in the gastrointestinal tract of mammals is due to the presence of secretory IgA antibodies. Antibody specificities have been detected in the secretory IgA of gut secretions to a wide range of naturally occurring viral and bacterial components and to test antigens such as chemically modified proteins. Much of the IgA found in gut secretions is synthesized and secreted locally by the abundant plasma cells of the lamina propria. Development of methods for establishing local protective immunity in the gut requires knowledge of the origins of these plasma cells and of the whereabouts of their precursors when they are susceptible to antigen-driven proliferation and/or maturation. The Peyer's patches have been shown to contain a population of B lymphocytes especially rich in precursors for IgA plasma cells and in cells which can repopulate gut lamina propria with such IgA plasma cells. The Peyer's patches also appear to 'sample' gut antigens, in that small amounts of antigens are passed intact through their dome epithelial cells. Recent experiments bearing on the origins, differentiation and maturation, antigen sensitivity, migration and lodging of precursors for gut IgA plasma cells are discussed. We use the following three systems: (1) congenic transfer of cells from different murine lymphoid cell sources or mixtures of these (CB20 leads to BALB/c or BALB/c leads to CB20) and the use of allo-antisera to IgA allotypic determinants to assess their potential to impart an adoptive IgA antibody response to the recipient and to repopulate its histocompatible lamina propria with IgA plasma cells; (2) clonal precursor analysis (the method of Klinman) both to enumerate antigen-sensitive cells in different tissues of mice and to evaluate their potential to generate plasma cells making particular isotypes and idiotypes of antibodies; (3) use of pairs of Thiry-Vella loops in rabbits, each member either bearing or lacking a Peyer's patch, and quantitation of antibodies of each isotype and of total secretory IgA to assess the response of each loop with the time after local immunization. The results from all three systems provide strong evidence for the importance of Peyer's patches in supplying cells responsible for local humoral immunity and suggest both a differentiative pathway for IgA precursors and their whereabouts when antigen may cause the expansion of a population of specific cells.

Research paper thumbnail of Studies on T cell clonal expansion. I. Suppression of killer T cell production in vivo

Journal of immunology (Baltimore, Md. : 1950), 1975

Adult C57BL/6 mice immunized i.p. with an allogeneic mastocytoma cell line (P815 of the DBA/2 str... more Adult C57BL/6 mice immunized i.p. with an allogeneic mastocytoma cell line (P815 of the DBA/2 strain) develop cytolytically active T cells. Activity peaks at 10 to 11 days and falls rapidly thereafter. We have observed an anomalous in vitro behavior of effector cell populations harvested during this decline. The lytic activity of spleen cells harvested 12 to 18 days after alloantigen was markedly augmented after culture for 24 hr at 37 degrees C. The augmented lytic activity was caused by T cells and specificity exhibited was identical to the pre-culture population. No augmentation of lytic activity occurred when cells were cultured at 4 degrees C or when they were treated with a protein synthetic inhibitor (pactamycin) at concentrations which did not compromise cytotoxic expression by the starting population. Augmentation of cytolysis was independent of DNA synthesis and did not require the presence of added antigen. When immune lymphoid cell populations were depleted of effector c...

Research paper thumbnail of Route‐Related Variation in the Immunogenicity of Killed Salmonella enteritidis Vaccine: Role of Antigen Presenting Cells

Microbiology and Immunology, 1989

In order to assess the role of the route of immunization on the immunogenicity of killed Salmonel... more In order to assess the role of the route of immunization on the immunogenicity of killed Salmonella vaccine, mice were immunized with killed S. enteritidis by intraperitoneal (i.p.) and intradermal (i.d.) routes. Whereas the former was non‐immunogenic, the i.d. immunization generated an excellent delayed‐type hypersensitivity response; further, i.p. immunization could even suppress the subsequent i.d. immunization. Since the peritoneal macrophages (MO) are known to be particularly low in Ia or MHC‐class II antigens, so essential for antigen presentation, the non‐immunogenicity by i.p. route was thought to be due to their poor presentation efficiency. Poly I: poly C, an interferon inducer, is known to enhance the MHC‐class II expression; hence effect of poly I: poly C treatment on the immunogenicity of the killed vaccine by i.p. route was tested and indeed the non‐immunogenicity was corrected. Poor efficiency of presentation of S. enteritidis antigen by peritoneal cells and its impro...

Research paper thumbnail of Murine CD8+ T suppressors against mycobacterial 65‐kDa antigen compete for IL‐2 and show lack of major histocompatibility complex‐imposed restriction specificity in antigen recognition

European Journal of Immunology, 1993

The mechanism of antigen‐specific suppression and reasons for aberrant major histocompatibility c... more The mechanism of antigen‐specific suppression and reasons for aberrant major histocompatibility complex (MHC) class II restriction mediated by CD8+ T cells was investigated in a previously reported murine model of immunosuppression, generated by intraperitoneal priming with Mycobacterium vaccae. Both the CD4+ T helper cells (Th) and CD8+ T supressor cell (Ts) of M.vaccae‐primed mice recognized the 65‐kDa antigen of the bacillus, presented by I‐A and I‐E, respectively. The CD8+ Ts could inhibit non‐antigen‐specific proliferation of primed CD4+ T cells induced by the exogenously added interleukin (IL)‐2 (concanvalin A‐stimulated culture supernatant). For inhibition, the Ts had to be activated by the 65‐kDa antigen. The degree of inhibition was dependent upon the amount of added IL‐2 and the relative numbers of primed CD8+ and CD4+ T cells. On incubation with antigen‐presenting cells, and the 65‐kDa antigen, the primed CD8+ T cells absorbed IL‐2 as efficiently as primed CD4+ T cells. B...

Research paper thumbnail of Origin and Differentiation of Lymphocytes Involved in the Secretory IgA Response

Cold Spring Harbor Symposia on Quantitative Biology, 1977

... The Peyer's patches are situated in the mucosa of the mammalian small bowel and are anat... more ... The Peyer's patches are situated in the mucosa of the mammalian small bowel and are anatomi-cally distinct from the surrounding IgA plasma-cell-201 ... They also noted the appearance of ferritin-binding IgA cells in the gut lamina propria after 30 days (Crabb~ et al. ...

Research paper thumbnail of Studies on t cell clonal expansion. II. The in vitro differentiation of pre-killer and memory t cells

Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at variou... more Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at various stages of the immune response and cultured in vitro in the presence and absence of antigen. Killer T cell activity in immune spleens could not be demonstrated until 6 or 7 days after antigen, but spleen cells harvested as early as 3 or 4 days and cultured for 24 hr at 37 degrees C showed significant cytotoxicity. This increased activity was not augmented further by culturing with antigen. "Memory" T cells, whose in vitro differentiation into killer cells required the presence of antigen, could not be demonstrated until 9 or 10 days after alloantigenic stimulation. Once produced, however, these cells persisted for at least 6 months. Memory cells, like killer T cells bound avidly to homologous allogeneic monolayers. There were indications that the memory T cell pool was heterogeneous. On one hand, when cells harvested 10 days after stimulation were exposed to antigen in vitro, their lytic activity increased within 24 hr but showed no further increases when the culture period was extended. In contrast, 45-day-old immune cells showed increasing lytic activity throughout a 4-day exposure to antigen. Augmentation of lytic activity in both cell populations was independent of DNA synthesis through the first 24 hr of culture. Subsequent increases in the activity of 45-day cells was dependent upon cell proliferation. Both the antigen-independent augmentation of lytic activity which followed culturing of immune cells, and the antigen-induced differentiation of memory cells were reversibly inhibited by a series of drugs which raised lymphocyte cAMP levels.

Research paper thumbnail of Studies on T Cell Clonal Expansion

The Journal of Immunology

Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at variou... more Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at various stages of the immune response and cultured in vitro in the presence and absence of antigen. Killer T cell activity in immune spleens could not be demonstrated until 6 or 7 days after antigen, but spleen cells harvested as early as 3 or 4 days and cultured for 24 hr at 37°C showed significant cytotoxicity. This increased activity was not augmented further by culturing with antigen. “Memory” T cells, whose in vitro differentiation into killer cells required the presence of antigen, could not be demonstrated until 9 or 10 days after alloantigenic stimulation. Once produced, however, these cells persisted for at least 6 months. Memory cells, like killer T cells bound avidly to homologous allogeneic monolayers. There were indications that the memory T cell pool was heterogeneous. On one hand, when cells harvested 10 days after stimulation were exposed to antigen in vitro, their lytic activi...

Research paper thumbnail of Studies on T Cell Clonal Expansion

The Journal of Immunology

Adult C57BL/6 mice immunized i.p. with an allogeneic mastocytoma cell line (P815 of the DBA/2 str... more Adult C57BL/6 mice immunized i.p. with an allogeneic mastocytoma cell line (P815 of the DBA/2 strain) develop cytolytically active T cells. Activity peaks at 10 to 11 days and falls rapidly thereafter. We have observed an anomalous in vitro behavior of effector cell populations harvested during this decline. The lytic activity of spleen cells harvested 12 to 18 days after alloantigen was markedly augmented after culture for 24 hr at 37°C. The augmented lytic activity was caused by T cells and specificity exhibited was identical to the pre-culture population. No augmentation of lytic activity occurred when cells were cultured at 4°C or when they were treated with a protein synthetic inhibitor (pactamycin) at concentrations which did not compromise cytotoxic expression by the starting population. Augmentation of cytolysis was independent of DNA synthesis and did not require the presence of added antigen. When immune lymphoid cell populations were depleted of effector cells by adsorpti...

Research paper thumbnail of Immunomodulatory properties of porins of some members of the family Enterobacteriaceae

Infection and Immunity, 1997

The outer membrane protein (OMP) preparation of Salmonella typhi was observed to have several imm... more The outer membrane protein (OMP) preparation of Salmonella typhi was observed to have several immunomodulatory properties. Treatment of mice with an intraperitoneal injection of the OMP preparation enhanced both cellular and humoral responses of the mice to an unrelated antigen, a killed vaccine of Mycobacterium vaccae; both the delayed-type hypersensitivity (DTH) response and the antibody titers were enhanced. The predominant isotype of the antibody shifted from immunoglobulin G1 (IgG1) to IgG2a upon treatment with OMP. Treatment of mice with the OMP preparation improved the efficiency of in vitro antigen presentation by the peritoneal cells and also induced the cells to secrete interleukin-1. Treatment with the lipopolysaccharide (LPS) preparation of S. typhi had the opposite effect; i.e., the DTH response to M. vaccae was suppressed. Treatment with OMP neutralized the suppressive effects of LPS. The OMP preparation also had an enhancing effect on the innate immune mechanisms of t...

Research paper thumbnail of The Secretory Immunoglobulin A Response in the Gut

Biochemical Society Transactions, 1977

Humoral immunity manifest in the mammalian gut is often due to the presence there of sIgA (secret... more Humoral immunity manifest in the mammalian gut is often due to the presence there of sIgA (secretory immunoglobulin A) antibodies. A considerable proportion of antibodies of this immunoglobulin isotype are synthesized locally by plasma cells, which are abundant in intestinal lamina propria. B-lymphocyte precursors for IgAsecreting plasma cells ('IgA plasma cells') appear to derive from the Peyer's patches (aggregated lymphatic follicles) of the small intestine. The Peyer's patches of rabbits contain a subpopulation of B-lymphocytes that can repopulate the spleen and lamina propria of irradiated allogeneic recipients with IgA plasma cells (Craig & Cebra, 1971). Pokeweed mitogen stimulates this subpopulation in vitro to generate IgA plasma cells (Jones et al., 1974). The immediate precursors for IgA plasma cells have been isolated in the subpopulation of Peyer's-patch cells bearing membrane Fab, and lacking membrane IgM by fluorescence-activated cell-sorting (Jones et al., 1974; Jones & Cebra, 1974). In addition to supplying precursors for IgA plasma cells, an 'antigen-sampling' role has been ascribed to Peyer's patches (Bockman & Cooper, 1973). Whole protein molecules may pass intact across their specialized dome epithelial cells and arrive in the midst of B-lymphocyte follicles. Thus IgA precursors may have their first encounter with antigen in the Peyer's patches, be stimulated to divide, and migrate in lymph/blood to intestinal lamina propria and generate plasma cells. We have devised an adoptive transfer system to compare the antigen-sensitivity of Peyer's-patch cells with cells from peripheral lymph nodes and spleen (Cebra et al., 1977a,b). Syngeneic or congeneic (CB20+Balb/c) cells were transferred into sublethally irradiated (600rad) recipients which were then challenged 1 day later with 5 x lo8 sheep erythrocytes. Antibody-forming cells in the recipients' spleens were enumerated at various times thereafter by the Jerne plaque assay and by facilitating antisera to distinguish cells making IgM, IgGl, IgG2 and IgA isotopes. Fluorochrome-labelled alloantisera, which distinguished IgA from CB20 (Ig-2*) and Balb/c (Ig-2") congeneic mice, were used to determine the origin of IgA plasma cells in recipient mice. The Peyer's-patch cells were as effective in adoptively transferring IgM and IgG responses as cells from peripheral lymph nodes or spleen. However, only Peyer's-patch cells transferred a significant IgA response, which began at about day 10 after transfer and reached a maximum of IgA Vol. 5

Research paper thumbnail of The secretory IgA System of the Gut

Novartis Foundation Symposia, 2008

Most commonly, humoral immunity manifested in the gastrointestinal tract of mammals is due to the... more Most commonly, humoral immunity manifested in the gastrointestinal tract of mammals is due to the presence of secretory IgA antibodies. Antibody specificities have been detected in the secretory IgA of gut secretions to a wide range of naturally occurring viral and bacterial components and to test antigens such as chemically modified proteins. Much of the IgA found in gut secretions is synthesized and secreted locally by the abundant plasma cells of the lamina propria. Development of methods for establishing local protective immunity in the gut requires knowledge of the origins of these plasma cells and of the whereabouts of their precursors when they are susceptible to antigen-driven proliferation and/or maturation. The Peyer's patches have been shown to contain a population of B lymphocytes especially rich in precursors for IgA plasma cells and in cells which can repopulate gut lamina propria with such IgA plasma cells. The Peyer's patches also appear to 'sample' gut antigens, in that small amounts of antigens are passed intact through their dome epithelial cells. Recent experiments bearing on the origins, differentiation and maturation, antigen sensitivity, migration and lodging of precursors for gut IgA plasma cells are discussed. We use the following three systems: (1) congenic transfer of cells from different murine lymphoid cell sources or mixtures of these (CB20 leads to BALB/c or BALB/c leads to CB20) and the use of allo-antisera to IgA allotypic determinants to assess their potential to impart an adoptive IgA antibody response to the recipient and to repopulate its histocompatible lamina propria with IgA plasma cells; (2) clonal precursor analysis (the method of Klinman) both to enumerate antigen-sensitive cells in different tissues of mice and to evaluate their potential to generate plasma cells making particular isotypes and idiotypes of antibodies; (3) use of pairs of Thiry-Vella loops in rabbits, each member either bearing or lacking a Peyer's patch, and quantitation of antibodies of each isotype and of total secretory IgA to assess the response of each loop with the time after local immunization. The results from all three systems provide strong evidence for the importance of Peyer's patches in supplying cells responsible for local humoral immunity and suggest both a differentiative pathway for IgA precursors and their whereabouts when antigen may cause the expansion of a population of specific cells.

Research paper thumbnail of Studies on T cell clonal expansion. I. Suppression of killer T cell production in vivo

Journal of immunology (Baltimore, Md. : 1950), 1975

Adult C57BL/6 mice immunized i.p. with an allogeneic mastocytoma cell line (P815 of the DBA/2 str... more Adult C57BL/6 mice immunized i.p. with an allogeneic mastocytoma cell line (P815 of the DBA/2 strain) develop cytolytically active T cells. Activity peaks at 10 to 11 days and falls rapidly thereafter. We have observed an anomalous in vitro behavior of effector cell populations harvested during this decline. The lytic activity of spleen cells harvested 12 to 18 days after alloantigen was markedly augmented after culture for 24 hr at 37 degrees C. The augmented lytic activity was caused by T cells and specificity exhibited was identical to the pre-culture population. No augmentation of lytic activity occurred when cells were cultured at 4 degrees C or when they were treated with a protein synthetic inhibitor (pactamycin) at concentrations which did not compromise cytotoxic expression by the starting population. Augmentation of cytolysis was independent of DNA synthesis and did not require the presence of added antigen. When immune lymphoid cell populations were depleted of effector c...

Research paper thumbnail of Route‐Related Variation in the Immunogenicity of Killed Salmonella enteritidis Vaccine: Role of Antigen Presenting Cells

Microbiology and Immunology, 1989

In order to assess the role of the route of immunization on the immunogenicity of killed Salmonel... more In order to assess the role of the route of immunization on the immunogenicity of killed Salmonella vaccine, mice were immunized with killed S. enteritidis by intraperitoneal (i.p.) and intradermal (i.d.) routes. Whereas the former was non‐immunogenic, the i.d. immunization generated an excellent delayed‐type hypersensitivity response; further, i.p. immunization could even suppress the subsequent i.d. immunization. Since the peritoneal macrophages (MO) are known to be particularly low in Ia or MHC‐class II antigens, so essential for antigen presentation, the non‐immunogenicity by i.p. route was thought to be due to their poor presentation efficiency. Poly I: poly C, an interferon inducer, is known to enhance the MHC‐class II expression; hence effect of poly I: poly C treatment on the immunogenicity of the killed vaccine by i.p. route was tested and indeed the non‐immunogenicity was corrected. Poor efficiency of presentation of S. enteritidis antigen by peritoneal cells and its impro...

Research paper thumbnail of Murine CD8+ T suppressors against mycobacterial 65‐kDa antigen compete for IL‐2 and show lack of major histocompatibility complex‐imposed restriction specificity in antigen recognition

European Journal of Immunology, 1993

The mechanism of antigen‐specific suppression and reasons for aberrant major histocompatibility c... more The mechanism of antigen‐specific suppression and reasons for aberrant major histocompatibility complex (MHC) class II restriction mediated by CD8+ T cells was investigated in a previously reported murine model of immunosuppression, generated by intraperitoneal priming with Mycobacterium vaccae. Both the CD4+ T helper cells (Th) and CD8+ T supressor cell (Ts) of M.vaccae‐primed mice recognized the 65‐kDa antigen of the bacillus, presented by I‐A and I‐E, respectively. The CD8+ Ts could inhibit non‐antigen‐specific proliferation of primed CD4+ T cells induced by the exogenously added interleukin (IL)‐2 (concanvalin A‐stimulated culture supernatant). For inhibition, the Ts had to be activated by the 65‐kDa antigen. The degree of inhibition was dependent upon the amount of added IL‐2 and the relative numbers of primed CD8+ and CD4+ T cells. On incubation with antigen‐presenting cells, and the 65‐kDa antigen, the primed CD8+ T cells absorbed IL‐2 as efficiently as primed CD4+ T cells. B...

Research paper thumbnail of Origin and Differentiation of Lymphocytes Involved in the Secretory IgA Response

Cold Spring Harbor Symposia on Quantitative Biology, 1977

... The Peyer's patches are situated in the mucosa of the mammalian small bowel and are anat... more ... The Peyer's patches are situated in the mucosa of the mammalian small bowel and are anatomi-cally distinct from the surrounding IgA plasma-cell-201 ... They also noted the appearance of ferritin-binding IgA cells in the gut lamina propria after 30 days (Crabb~ et al. ...

Research paper thumbnail of Studies on t cell clonal expansion. II. The in vitro differentiation of pre-killer and memory t cells

Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at variou... more Spleen cells from C57BL/6 mice immunized with a DBA/2 mastocytoma (P815) were harvested at various stages of the immune response and cultured in vitro in the presence and absence of antigen. Killer T cell activity in immune spleens could not be demonstrated until 6 or 7 days after antigen, but spleen cells harvested as early as 3 or 4 days and cultured for 24 hr at 37 degrees C showed significant cytotoxicity. This increased activity was not augmented further by culturing with antigen. "Memory" T cells, whose in vitro differentiation into killer cells required the presence of antigen, could not be demonstrated until 9 or 10 days after alloantigenic stimulation. Once produced, however, these cells persisted for at least 6 months. Memory cells, like killer T cells bound avidly to homologous allogeneic monolayers. There were indications that the memory T cell pool was heterogeneous. On one hand, when cells harvested 10 days after stimulation were exposed to antigen in vitro, their lytic activity increased within 24 hr but showed no further increases when the culture period was extended. In contrast, 45-day-old immune cells showed increasing lytic activity throughout a 4-day exposure to antigen. Augmentation of lytic activity in both cell populations was independent of DNA synthesis through the first 24 hr of culture. Subsequent increases in the activity of 45-day cells was dependent upon cell proliferation. Both the antigen-independent augmentation of lytic activity which followed culturing of immune cells, and the antigen-induced differentiation of memory cells were reversibly inhibited by a series of drugs which raised lymphocyte cAMP levels.