Antigen-specific suppression of cytotoxic T cell responses in mice. I. Suppressor T cells are not cytotoxic cells (original) (raw)
1978, European Journal of Immunology
The main conclusion from these experiments is that the antigen-specific suppressor T cell of mice which inhibits the induction of cytotoxic T lymphocytes is not itself a cytotoxic T cell. This conclusion is supported by two main observations: first, a certain cell number from first-step cultures which was suppressive in the presence of a high dose of antigen actually helped the cytotoxic response at a lower antigen dose. This observation is difficult t o reconcile with the hypothesis that suppression is due to the killing of the stimulator or the responder cells in the second-step culture by cytotoxic T cells. Second, cells from first-step cultures of cortisone-treated mice displayed cytotoxic activity but had no suppressive effect on the generation of killer cells. It was further demonstrated that these cells failed to influence in any way the suppressive effect, however weak, of cells from first-step cultures of normal spleen. We therefore favor the view that the suppression observed in this system is due to a regulatory signal which occurs as a result of the ability of both inhibitory cells and responder cells to recognize and respond to allogeneic determinants expressed on the surface of stimulator cells. The suppressor T cells described here act by linked associative recognition of antigen. That is, suppressor T cells only inhibit the induction of a precursor cytotoxic T cell in the presence of an antigen to which both the precursor cell and the suppressor cell can bind. In this sense, suppressors act in a manner analogous to helper T cells in T-B cell cooperation; carrier-specific helper T cells only enhance an anti-hapten B cell response in the presence of hapten-carrier conjugates. Similarly, alloantigen a (carrier)-specific suppressor T cells only inhibit alloantigen b (hapten)-specific cytotoxic responses in the presence of (a x b)F1 stimulator cells (hapten-carrier conjugate), not in the presence of a mixture of parental stimulator cells (a + b).
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T cell independent induction of antigen specific suppression of the antibody response
La Ricerca in clinica e in laboratorio
Immune spleen cells (from mice given 2 x 10(7) HRBC 14 days earlier) when mixed in vitro with carrier-primed syngeneic spleen cells (from mice given 2 x 10(5) HRBC 3 days earlier) are able to suppress the anti-TNP and anti-HRBC PFC response to TNP-HRBC. If immune thymocytes are substituted for spleen cells suppression is not observed. This suppression is antigen specific, resistant to anti-T treatment or x-irradiation, and is exerted by nylon wool-retained cells of the immune spleen cell population. An antigen specific suppressive factor is released from immune spleen cells in culture. Under these experimental conditions, suppression appears to be mediated by a specific product of B rather than T cells present in the immune spleen cell population.
The distinctive specificity of antigen-specific suppressor T cells
Immunology Today, 1991
Although suppressor T cells have been cloned in only a few instances, the existence of a functional cadre ofT cells that acts to downregulate the immune response is well documented. In this review Eli Sercarz and Urszula Krzych describe studies on suppressor T-cell (Ts-cell) specificity that provide some support for the conclusion that the T s cell is a distinctive cell type with an expressed repertoire that is different from that expressed by helper T (TIq) cells. They go on to explore the interaction between cells recognizing Ts-cell-inducing determinants (SDs) and TH-cell-inducing determinants (HDs), and their relationship to immunogenicity and Ir gene effects. In addressing the question of the specificity of T cells with suppressive function, a distinction must first be drawn between CD8 + and CD8-suppressor T cells. In both mouse and human systems, the distincnon between CD4 + suppressor inducer T (Tst) cells and CD8 + suppressor precursor T (or the effector cells themselves, TsE cells) cells has been clearly made; the inducer Tst cells have been shown to be necessary for activation of precursors of the effector cell, TsE 1,2. Likewise, the expression of different surface markers by CD4 + Trt and CD4 + Tst cells correlates with the functional disparity of these cells 3, although there is evidence that the CD4 + Tsl cells may be a late stage of the CD4 + helper T cell and may, therefore, be expected to have the identical specificity for antigen. This review is restricted to the specificity of 'professional' CD8 + Ts-cell precursors and effectors for nominal protein antigens whose primary structures have been defined, and their specificity relationships to CD4 + cells. The specificity of CD4 + 'nonprofessionals' such as TH1 and Trt2 cells, which do exhibit mutually inhibitory, cytokine-related suppressive activities 4-6 will not be considered nor will the interesting generalization that mouse and human Tst cells are E(DQ)-restricted rather than A(DR)-restricted be discussed 7,8. Criteria for defining SDs Induction by fragments or peptides from the antigen The first report that a portion of a Ts-cell-inducing protein antigen could substitute for the whole molecule in the induction of suppressor T cells concerned Escherichia coli 13-galactosidase (GZ)9,1°: a cyanogen bromide peptide of GZ, CB-2 (amino acids 3-92), induced Ts cells that could nullify, in vitro, the antibody response to the hapten fluorescein within the antigen GZfluorescein isothiocyanate (FITC), as demonstrated in cell-mixing experiments with GZ-primed helper T cells. Simultaneously, analysis of the anti-hen egg lysozyme (HEL) response in a nonresponder mouse strain (C57BL/6, H-2 b) produced evidence that a proteolytic fragment (N-C = 1-17: Cys6-Cys127: 120-129) from HEL could mimic the native molecule in the induction of suppression 11. This supported the concept that Phe3 was important for the induction of suppression, based on the
Cellular Immunology, 1986
Previous studies demonstrated that the first-order T-suppressor factor (TsF,) requires the presence of antigen to induce idiotype-specific Ts cells which readily suppress phenyltrimethylamino (TMA) hapten-specific delayed-type hypersensitivity (DTH) responses when transferred into already immune recipients. In this study we show that TsF, in the absence of antigen induces a splenic population which limits DTH in recipient mice only when an additional accessory lymphoid population was also cotransferred. Neither of these populations alone was sufficient to mediate suppression and depletion of T cells in either population's abrogated suppression, indicating the T-cell dependency of the complementing cell types. Moreover, suppression was seen only when TMA-TsF,-induced and not normal spleen cell lysate-induced cells were cotransferred with the antigen-induced population, suggesting the requirement for a specific signal to induce the factor-induced population. Further experiments showed that the antigen-induced lymphoid population could be replaced by either heterologous antigen-induced or adjuvant alone-induced splenic populations, indicating the lack of specificity of this secondary population. Further analysis showed that the cell complementation between TMA-TsF,-induced and the nonspecific accessory lymphoid population resulted in antigen-specific and genetically restricted immune suppression. The TsFi-induced lymphoid population was not responsible for the genetic restriction, and furthermore, there was no restriction observed between the two complementing populations. However, matching of the nonspecific accessory cell with the recipient host at the I-J subregion of the H-2 complex was essential for immune suppression. Finally, the activity of complementing cells was found to be independent of cyclophosphamide-sensitive Ts populations of the recipient mice. The ramifications of these findings with reference to the existing suppressor pathways are discussed. 0 1986 Academic press, IIK.
Special attractions for suppressor T cells
Trends in Immunology, 2003
After over a decade of eclipse, suppressor T (Ts) cells have regained a reputation as key controllers of peripheral immunological self-tolerance. This Opinion focuses on recent advances in understanding the trafficking and tissue localization of CD25 1 CD4 1 T cells, the best characterized population of naturally occurring Ts cells. Their distinct homing preferences and selective responsiveness to specific chemokines help in defining their role in physiological and pathological immune responses, and could offer the possibility of developing novel therapies for immunomodulation.
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