Interleukin 10 protects activated human T lymphocytes against growth factor withdrawal-induced cell death but only anti-fas antibody can prevent activation-induced cell death.
Interleukin 10 (IL-10) is a pleiotropic T cell-derived cytokine best known for its negative regulatory effects on T cell immunity. It inhibits responses indirectly by downregulating expression of major histocompatibility complex (MHC) molecules and co-stimulatory molecules such as CD80 on antigen presenting cells as well as directly via its effects on responding cells. On the other hand, IL-10 has been shown to protect activated T cells against apoptosis caused by withdrawal of the major growth factor, IL-2, and allow proliferation of T cells in the absence of IL-2. However, we show here that this IL-10-dependent, IL-2-independent proliferative response is short-lived, and that IL-10-responsive T cells cannot multiply in its presence. Moreover, inclusion of exogenous IL-10 in clonal cultures propagated with IL-2 results in suppression of their growth. These findings, together with the observation that IL-10 fails to protect T cells against activation-induced cell death (a fas/fas-ligand-dependent phenomenon blocked only by certain antagonistic anti-fas reagents), suggest that the negative regulatory effects of IL-10 outweigh the upregulated proliferation observed on some T cell clones (TCC) in the absence of IL-2.
Pawelec
G
G
Second Department of Internal Medicine, University of Tübingen MedicalSchool, Federal Republic of Germany. graham.pawelec@uni-tuebingen.de
Hambrecht
A
A
Rehbein
A
A
Adibzadeh
M
M
D000906:Antibodies / Q000276:immunology; D017209:Apoptosis; D002455:Cell Division; D002478:Cells, Cultured; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D000906:Antibodies; D006133:Growth Substances; D007376:Interleukin-2; D019014:fas Receptor; D016753:Interleukin-10