Murine neonatal spleen contains natural T and non-T suppressor cells capable of inhibiting adult alloreactive and newborn autoreactive T-cell proliferation (original) (raw)
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Cellular Immunology, 1991
Mitogen-stimulated spleen cells from newborn mice do not synthesize mRNA for the 55-kDa interleukin-2 receptor (IL-2R). The kinetic of development after birth of ability to synthesize IL-2R correlated well with the functional immaturity of T cells, as was tested by responsiveness to T-cell mitogen concanavalin A (Con A). This functional immaturity of T cells was not due to the activity of neonatal suppressor cells (NSC) which inhibited immune responses induced by mitogens or antigens. The suppressor cells did not inhibit proliferation of spleen cells stimulated with IL-1 or IL2, nor did they inhibited expression of genes for tumor necrosis factor (TNF)-& TNF-ol, and IL-2R in stimulated cells from adult mice. The results thus show functional immaturity of T cells in newborn mice and selectivity of the immunosuppressive action of NSC, which allow for production and for functional activity of cytokines at a time when the specific immune system is not functional because of both immaturity and a selective activity of inhibitory cells. o 1991 Academic Press, Inc.
Ly phenotype and mechanism of action of mouse neonatal suppressor T cells
Journal of Experimental Medicine, 1977
Neonatal suppressor T cells were isolated from the thymuses of 10- to 14-day old BDF mice infected at birth with mouse thymic virus. Such cells were enriched for suppressive activity directed against antibody formation by adult B cells and represented a relatively homogenous population of outer cortical cells. Their surface antigen phenotype was found to be: Ly 1+, Ly 2+, TL+, Thy 1+, and H-2+. The cells were larger and contained more DNA than thymocytes from age-matched controls. These findings identify neonatal suppressor T cells as a unique subpopulation separate from most inducible suppressor cells in the adult mouse. The mechanism of action of neonatal suppressor T cells seems to be a reduction in the number of B cells initially triggered by antigen.
Journal of Experimental Medicine, 1975
The relative functional maturity of neonatal mouse spleen T- and B-cell populations was assessed by comparing the ability to respond to the thymic-independent antigen, DNP-Ficoll, or thymic-dependent SRBC by producing antibody in vitro. Although mouse spleen cells responded to DNP-Ficoll at an earlier age than they responded to SRBC or TNP-SRBC, the reason for the lag in the T-dependent response was confounded by the finding of high numbers of suppressor T lymphocytes in the neonatal spleen. Thus, small numbers of neonatal spleen T cells or thymocytes significantly decreased the in vitro antibody response of adult spleen cells. Although B lymphocytes appear to be functionally mature soon after birth, their acitivity may be modulated by an excess of suppressor T cells; e.g., the reconstitution of helper cell function in the neonatal spleen required anti-theta treatment before addition of adult helper cells. Suppressive activity attributable to T cells seems to play a dominant role in...
Analysis of Neonatal T Cell and Antigen Presenting Cell Functions
Human Immunology, 1997
Neonates are more susceptible to infection than adults and exhibit more intense or prolonged clinical symptoms. The extent to which deficiencies in T cell or antigen presenting cell (APC) function underlie hyporesponsiveness is incompletely understood. Here, immune function of cord blood mononuclear cells (CBMC), from healthy, full-term neonates was compared with adult PBMC. As widely reported, polyclonally-stimulated T cell proliferation was found to be equivalent, while IFN gamma responses were markedly lower amongst neonates. Reasoning that such stimuli may elicit responses qualitatively different from those that would be obtained following MHC-dependent, cognate T cell activation, alloantigen-specific responses were evaluated. Strikingly, neonates exhibited IFN gamma, IL-4 and IL-10 production equal to adults in short term primary culture. Both the frequency (Fisher's p < 0.0004) and intensity (< 7.5 vs 36.5 pg/ml; Wilcoxon P = 0.005) of alloantigen stimulated IL-5 responses were elevated among neonates, a finding equally evident using irradiated adult or neonatal cells as stimulators. Finally, the relative capacity of neonatal APC as stimulators of cytokine synthesis was assessed by a novel approach using CBMC as both responders and stimulators in MLR. Irradiated neonatal cells consistently stimulated similar proliferative but substantially lower IFN gamma responses than did adult APC, independent of responder origin. The data argue; (i) T cells are largely immunocompetent at birth, (ii) accessory cell function is not fully mature, and (iii) the widely observed hyporesponsiveness to pathogenes may be primarily due to immaturity of APC function or costimulator molecule expression.
Fetal and Postnatal Development of T-lymphocyte Subpopulations
Acta Veterinaria Brno, 2002
Changes in individual subpopulations of lymphocytes (mainly CD2 + , CD4 + and CD8 +) in primary and secondary lymphatic organs and circulating blood were observed in pig fetuses between days 51 and 112 of gestation, and in circulating blood in postnatal piglets. The technique of flow cytofluorimetry was used and binding of specific monoclonal antibodies was visualised using polyclonal antibodies against mouse or rat Ig marked with fluorochroms (PE and FITC). As soon as on day 51 of gestation, CD4 + and CD8 + T lymphocytes were demonstrated in porcine thymus. Their relative and actual numbers continued to increase markedly. When this increase was expressed in terms of age with subsequent intrapolation, the changes in CD4 + /CD8 + phenotype expression could be expected around day 40, i.e. in the period, when thymus cortex and medulla are not yet morphologically differentiated. In the spleen only CD2 + cells were found on day 51 of gestation. Expression of lymphocytes with CD4 + and CD8 + receptors was shown on day 60. Their relative and actual numbers increased with age. This increase when expressed per whole organ made a difference of three orders of magnitude. In lymph nodes, only changes from day 90 were followed. In this secondary lymphatic organ, the percentage of T lymphocytes with CD4 + and CD8 + markers was higher than that in the spleen. The CD4 + /CD8 + ratio in spleen and thymus gradually decreased with advancing age to 1 with a slightly dominant CD4 + lymphocyte subpopulation. On the other hand, in lymph nodes of pig fetuses CD8 + lymphocytes prevailed (index 0.85). In the postnatal period, a marked increase of cytotoxic CD8 + lymphocytes occurred in peripheral blood of 28-day-old piglets. Thus the CD4 + /CD8 + index decreased from 1 to 0.2. This characteristic of lymphocyte subpopulations in circulating blood is also typical of adult individuals. The numbers of B lymphocytes with IgM receptors in circulating blood increased gradually from day 90 of prenatal development until day 28 h of postnatal life both in relative and actual terms.
Restricted adult clonal profiles induced by neonatal immunization. Influence of suppressor T cells
Journal of Experimental Medicine, 1983
The effects of neonatal antigen exposure on the adult B cell repertoire have been examined by characterizing the influenza hemagglutinin (HA)-specific response of adult BALB/c mice given antigen soon after birth. Ligand exposure during early life exerts a profound and lasting effect upon the B cell repertoire, characterized by the expansion and preservation of particular antigen-reactive clones and the apparent loss of others. The precise subset of clonotypes selectively preserved depends upon the age at which antigen is first encountered; and is predictable given a knowledge of the emerging primary pool's dynamics and composition. The preserved (secondary) B cells differ from their unprimed precursors with respect to (a) expression of the surface marker detected by the monoclonal antibody J11d, and (b) susceptibility to T cell-mediated suppression. These studies thus demonstrate a strong relationship between the heritable dynamics of the emerging primary B cell repertoire and t...
Cellular Immunology, 1989
Expression of certain autologous lymphocyte-activating antigenic determinants on the developing embryo is known to provide a stimulus for maternal anti-fetal autoproliferative responses. If left unregulated these responses could exert negative influences on the reproductive process by converting to autoaggressive forms of immune reactivity. In normal circumstances, immunological reactions of this nature are therefore likely to be under the control of pregnancy-associated immunoregulatory elements found within the maternal/fetal environment. In the present investigation we describe a naturally occurring splenic inhibitory cell type devoid of conventional T, B, and macrophage surface markers associated with syngeneic murine pregnancy that is capable of exerting potent immunosuppressive effects on an in vitro expression of fetal/newborn T cell autoreactivity, namely the autologous mixed lymphocyte reaction (AMLR). Maternal spleen cells inhibitory for AMLR were found to be highly resistant to cytotoxic pretreatment with a panel of conventional antisera directed against T cell-specific antigenic determinants. The non-T nature of the natural splenic suppressor cell was further indicated by experiments showing that purified spleen T cells had no inhibitory activity. Pregnancy spleen cell populations that were effectively depleted of macrophages retained full ability to inhibit AMLR. Maternal suppressor activity could be localized to the spleen cell population bearing receptors for the B cell-specific lectin, soybean agglutinin (SBA). A panel of monoclonal antibodies prepared against enriched populations of suppressor cells was screened and selected for specific reactivity using an ELISA against glutaraldehyde-fixed SBA+ spleen cell subpopulations from pregnant versus virgin animals. Several of the monoclonals developed against suppressor-enriched spleen cell populations from &pregnant as well as allopregnant animals were effective in reducing or eliminating suppressor cell activity following cytotoxic pretreatment in the presence of complement. The novel set of anti-suppressor monoclonal antibodies described here should prove useful in furthering the isolation and characterization of pregnancy-associated suppressor cells and in determining their relationship to natural suppressor cell populations described in other Systems.