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The Journal of Immunology, 2001, 167: 773-778.
Copyright © 2001 by The American Association of Immunologists

Regulation of TGF-{beta} Response During T Cell Activation Is Modulated by IL-101

Françoise Cottrez and Hervé Groux2

Institut National de la Santé et de la Recherche Médicale, Unité 343, Nice, France

TGF-{beta}1 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-{beta}1 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-{beta}1 on CD4+ T cell activation by evaluating the effect of TGF-{beta}1 on the proliferative and cytokine responses of purified resting and activated human or mouse CD4+ T cells. TGF-{beta}1 inhibits proliferation and cytokine secretion on resting CD4+ T cells but has no inhibitory effect on activated T cells. Moreover, TGF-{beta}1 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.




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