Regulation of TGF-beta response during T cell activation is modulated by IL-10.
TGF-beta1 is an important pleiotropic cytokine that has been described to have both stimulatory and inhibitory effects on cell growth and differentiation. For several cell types, the effect of TGF-beta1 was found to correlate with the differentiation stage of the cells and the presence of other cytokines. In this report, we address the influence of TGF-beta1 on CD4(+) T cell activation by evaluating the effect of TGF-beta1 on the proliferative and cytokine responses of purified resting and activated human or mouse CD4(+) T cells. TGF-beta1 inhibits proliferation and cytokine secretion on resting CD4(+) T cells but has no inhibitory effect on activated T cells. Moreover, TGF-beta1 unresponsiveness of activated T cells was correlated with a down-regulation in the expression of the TGF-beta receptor type II. Interestingly, IL-10 addition enhances TGF-beta receptor type II expression and restores TGF-beta responsiveness on activated T cells. These results indicated that TGF-beta responsiveness is sequentially regulated on T cells by the modulation of the of TGF-beta receptor type II chain expression. Moreover, we have identified a novel regulatory role of IL-10 on TGF-beta-dependent T cell growth that can explain the control of T cell activation on chronic vs acute inflammatory sites.
Cottrez
F
F
Institut National de la Santé et de la Recherche Médicale, Route de St. Antoine de Ginestière, Unité 343, Nice, France.
Groux
H
H
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D002999:Clone Cells; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II