EurekaMag.com logo
+ Site Statistics
References:
52,725,316
Abstracts:
28,411,598
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Regulation of in vitro cytotoxic t lymphocyte generation 3. interactions of regulatory t cell subsets in suppressor and target populations


JMCI (Journal of Molecular and Cellular Immunology) 1(4): 237-250
Regulation of in vitro cytotoxic t lymphocyte generation 3. interactions of regulatory t cell subsets in suppressor and target populations
During allogeneic mixed leukocyte cultures (MLC), cytotoxic T lymphocytes (CTL) and at least 2 kinds of suppressor T lymphocyte (Ts) functions are induced. One Ts, termed nonspecific (TsN), can suppress the in vitro generation of CTL when it is transferred to any allogeneic MLC. The other Ts has specificity for MLC in which stimulator cells are homologous at the major histocompatibility complex (MHC) with stimulator cells used to induce the Ts (TsS). Previously, it was shown that addition of a 10-4 M concentration of the histamine1 antagonist pyrilamine to the MLC strongly influences the kind of T cell function generated. The generation of CTL and TsN are inhibited while the induction of TsS is not. CTL precursors are activated (CTL-PA) in such cultures, as witnessed by their differentiating into CTL effectors upon removal of pyrilamine and transfer to a salubrious environment (e.g., any fresh MLC). This 2nd step in the differentiation of CTL can be prevented by exposure of pyrilamine-treated MLC derived cells to .gtoreq. 500 rad .gamma.-irradiation. Therefore, by using these combined in vitro manipulations, under the proper experimental conditions, it is possible to study TsS in the absence of both TsN and CTL. Antibodies to the cell surface alloantigens Lyt 1, Lyt 2 and TL/Qa-1 were used to study whether [mouse] TsN and TsS also can be separated by virtue of their having different cell surface phenotypes. The existence of interactions between subsets of T cells in the suppression of CTL generation and whether these interactions (circuits) are akin to those previously demonstrated to be important in the regulation of B cell responses to antigen were also studied. Since CTL generation likely is important in the host defense against viruses and other pathogens, neoplasms and transplants of foreign tissues, a firm understanding of regulatory interactions modifying this response is important. Negative selection with alloantigen-specific antibodies and complement (C') was used in this study. Immune Lyt 1+2+ (Ly 123) T lymphocytes are strongly involved in MLC-induced nonspecific suppression, but are not required for the expression of specific suppression. Rather, both immune Lyt 1+2- (Ly 1) and Lyt 1-2+ (Ly 2) T lymphocytes appear to be involved in optimal TsS function. TsN and TsS activities could not be separated using a serum that contains antibodies to Qa-1 and TL alloantigens; i.e., both Ts activities were removed by treating alloantigen-activated Ts with this serum and C'. Immune TsS often are not sufficient for the expression of suppression. In most experiments, suppression failed to occur if nonimmune Ly 123 cells had been removed from the target responding population. Suppression of only T helper cell precursors and/or CTL precursors of the Ly 123 phenotype cannot account for the results presented because in certain experiments, CTL generation by unfractionated responder cells was suppressed by TsS to a level that must include inhibition of virtually all CTL precursors in the population. These data are compatible with the existence of regulatory T cell interactions in CTL generation, which are similar to both feedback suppression and suppressor amplification circuits, that are active in the regulation of B lymphocyte responses.


Accession: 006288706



Related references

Regulation of in vitro cytotoxic T lymphocyte generation. III. Interactions or regulatory T cell subsets in suppressor and target populations. Journal of Molecular and Cellular Immunology 1(4): 237-252, 1984

Interactions between regulatory and target t cell populations in cyto toxic t lymphocyte generation. Federation Proceedings 41(3): ABSTRACT 2638, 1982

Regulatory mechanisms in cytotoxic T lymphocyte development. II. Dissociation of in vitro cytotoxic T-lymphocyte and suppressor T-cell activities with L-ornithine. Cellular Immunology 101(2): 512-523, 1986

Down-regulation of cytotoxic T lymphocyte generation by two distinct suppressor-cell systems. Annals of the New York Academy of Sciences 532: 177-198, 1988

Regulation of in vitro cytotoxic T lymphocyte generation. II. Demonstration of noncytotoxic alloantigen-specific suppressor T lymphocytes. European Journal of Immunology 12(5): 380-386, 1982

Immune status in crohns disease 6. immuno regulation evaluated by multiple distinct t suppressor cell assays of lymphocyte proliferation and by enumeration of immuno regulatory t lymphocyte subsets. Gastroenterology 86(6): 1531-1543, 1984

Regulatory mechanisms in cytotoxic T lymphocyte development. III. Induction, specificity, and genetic restriction of an in vitro suppressor T cell. Cellular Immunology 101(2): 524-533, 1986

Allograft immunity in vitro. V. Generation of cytotoxic effector cells in mixed lymphocyte culture and the specificity of target cell lysis. Cellular Immunology 8(3): 470-483, 1973

BCG-induced suppressor cells. I. Demonstration of a macrophage-like suppressor cell that inhibits cytotoxic T cell generation in vitro. Journal of Immunology 120(2): 563-569, 1978

Regulation of in vitro cytotoxic T lymphocyte generation. I. Evidence that killer cell precursors differentiate to effector cells in two steps. Journal of Experimental Medicine 155(3): 783-796, 1982