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Suppressive mechanisms in alloantigen-induced T cell responses
In this report we examined the possibility that suppression of the mixed lymphocyte response by MLR-TsF results from interference with IL- 2 regulation of T cell proliferation. Two distinct processes of inhibition involving both a direct effect on IL-2-driven proliferation of responder T cells, and...
Formato: | Texto |
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Lenguaje: | English |
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The Rockefeller University Press
1983
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2187162/ https://www.ncbi.nlm.nih.gov/pubmed/6227676 |
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collection | PubMed |
description | In this report we examined the possibility that suppression of the mixed lymphocyte response by MLR-TsF results from interference with IL- 2 regulation of T cell proliferation. Two distinct processes of inhibition involving both a direct effect on IL-2-driven proliferation of responder T cells, and induction of a second-order suppressor cell (Ts2) were described. Exogenous IL-2 did not abrogate MLR-TsF-induced suppression, and activated responder cells from suppressed cultures expressed functional IL-2 receptors by IL-2 adsorption analysis. Thus, suppression is not due to lack of available IL-2 or to abnormal acquisition of receptors for IL-2 during T cell activation. In contrast, a profound MLR-TsF effect on IL-2-induced proliferation of HT2 cells as well as MLR-activated cells was observed even after presaturation of receptors with excess IL-2. These results differentiated the direct responder cell effect of MLR-TsF from its Ts2 inductive capacity, and localized the defect in responder cell proliferation to events occurring subsequent to IL-2 binding. When analyzed in terms of proposed models for hormone-receptor interactions, characteristic dose-response curves similarly predict a postreceptor defect. Examination of the Ts2 pathway of suppression revealed a late- acting inhibitory effect peaking 72 h after MLR initiation. A minor part of Ts2 activity was susceptible to exogenous IL-2, and may reflect a requirement for IL-2 during Ts2 expansion. However, the most significant component of Ts2-mediated suppression was resistant to excess IL-2, and IL-2 production was normal in Ts2-regulated cultures, thus ruling out limitation of IL-2 for responder cell use as the major mechanism of Ts2 suppression. The complete pathway of Ts2 suppression and its functional relationship to other MLR-TsF inhibitory activities is not yet fully understood. However, these results suggest that the ultimate mechanisms of alloantigen-induced suppression involve late events of the IL-2-dependent lymphokine cascade. |
format | Text |
id | pubmed-2187162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1983 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21871622008-04-17 Suppressive mechanisms in alloantigen-induced T cell responses J Exp Med Articles In this report we examined the possibility that suppression of the mixed lymphocyte response by MLR-TsF results from interference with IL- 2 regulation of T cell proliferation. Two distinct processes of inhibition involving both a direct effect on IL-2-driven proliferation of responder T cells, and induction of a second-order suppressor cell (Ts2) were described. Exogenous IL-2 did not abrogate MLR-TsF-induced suppression, and activated responder cells from suppressed cultures expressed functional IL-2 receptors by IL-2 adsorption analysis. Thus, suppression is not due to lack of available IL-2 or to abnormal acquisition of receptors for IL-2 during T cell activation. In contrast, a profound MLR-TsF effect on IL-2-induced proliferation of HT2 cells as well as MLR-activated cells was observed even after presaturation of receptors with excess IL-2. These results differentiated the direct responder cell effect of MLR-TsF from its Ts2 inductive capacity, and localized the defect in responder cell proliferation to events occurring subsequent to IL-2 binding. When analyzed in terms of proposed models for hormone-receptor interactions, characteristic dose-response curves similarly predict a postreceptor defect. Examination of the Ts2 pathway of suppression revealed a late- acting inhibitory effect peaking 72 h after MLR initiation. A minor part of Ts2 activity was susceptible to exogenous IL-2, and may reflect a requirement for IL-2 during Ts2 expansion. However, the most significant component of Ts2-mediated suppression was resistant to excess IL-2, and IL-2 production was normal in Ts2-regulated cultures, thus ruling out limitation of IL-2 for responder cell use as the major mechanism of Ts2 suppression. The complete pathway of Ts2 suppression and its functional relationship to other MLR-TsF inhibitory activities is not yet fully understood. However, these results suggest that the ultimate mechanisms of alloantigen-induced suppression involve late events of the IL-2-dependent lymphokine cascade. The Rockefeller University Press 1983-12-01 /pmc/articles/PMC2187162/ /pubmed/6227676 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Suppressive mechanisms in alloantigen-induced T cell responses |
title | Suppressive mechanisms in alloantigen-induced T cell responses |
title_full | Suppressive mechanisms in alloantigen-induced T cell responses |
title_fullStr | Suppressive mechanisms in alloantigen-induced T cell responses |
title_full_unstemmed | Suppressive mechanisms in alloantigen-induced T cell responses |
title_short | Suppressive mechanisms in alloantigen-induced T cell responses |
title_sort | suppressive mechanisms in alloantigen-induced t cell responses |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2187162/ https://www.ncbi.nlm.nih.gov/pubmed/6227676 |