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Regulation of cytokine production by human Th0 cells following stimulation with peptide analogues: differential expression of TGF‐β in activation and anergy
Author(s) -
TSITOURA D. C.,
GELDER C. M.,
KEMENY D. M.,
LAMB J. R.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00319.x
Subject(s) - biology , cytokine , t cell , stimulation , microbiology and biotechnology , t cell receptor , antigen , transforming growth factor , cytotoxic t cell , immune system , secretion , immunology , biochemistry , endocrinology , in vitro
The different biological activities of T‐cell‐derived cytokines and their level of production influences the qualitative nature of immune responses and, in certain forms of T‐cell tolerance, the lack of antigen responsiveness is associated with the production of transforming growth factor‐& bgr; (TGF‐& bgr; ) and interleukin‐4 (IL‐4). In this study we have investigated the effects of T‐cell receptor (TCR) ligation with peptide analogues and the native peptide, in the presence and absence of costimulation, on cytokine production by human T‐helper type 0 (Th0) cells reactive with influenza virus haemagglutinin (HA) peptide (HA306–318) and restricted by HLA‐DRB1*0101. We observed that resting Th0 cells constitutively produced TGF‐& bgr; , but when stimulated with peptide and antigen‐presenting cells (APC) under conditions that induce clonal expansion, TGF‐& bgr; secretion was abrogated. Furthermore, exposure of the T cells to the wild‐type HA peptide under conditions that induce T‐cell anergy resulted in the secretion of TGF‐& bgr; , and subsequent antigenic rechallenge was unable to override this signal and down‐regulate TGF‐& bgr; production. Stimulation with altered TCR ligands that failed to induce proliferation also resulted in marked production of TGF‐& bgr; , although in many instances the levels were less than those observed in the total absence of antigen, suggesting that partial signalling has occurred. Although in general, there was a direct positive correlation between proliferation and the production of IL‐2, IL‐4 and interferon‐& ggr; (IFN‐& ggr; ) following stimulation with certain analogues, the production of selected cytokines was dissociated.