Immunosuppressive effects of transforming growth factor β: Inhibition of the induction of Ia antigen on Langerhans cells by cytokines and of the contact hypersensitivity response

Seth P. Epstein, Rudolf L. Baer, G. Jeanette Thorbecke, Donald V. Belsito

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52 Scopus citations

Abstract

Recent reports show that transforming growth factor (TGF)-β exerts a variety of immunosuppressive activities. The present study focuses on the effects of TGF-β1 on expression of Ia antigen by Langerhans cells. Although TGF-β1, in concentrations from 0.001 to 100 μg/ml, has no effect on constitutive expression of Ia antigen on these cells, the in vitro up-regulation of Ia antigen on the surface of LC by interleukin (IL)-1, tumor necrosis factor-α, interferon-γ, IL-3, and granulocyte/macrophage-colony stimulating factor is inhibited by the concommitant addition of 1 μg/ml TGF-β1. In contrast, TGF-β1 has no effect on the up-regulation induced by IL-2 or IL-6. In this report, the activity of TGF-β closely resembles that of Cyclosporine A (CsA). Similar results are seen in vivo when either TGF-β1 (5 μg, intraperitoneally [ip], daily on days 0-3) or CsA (1 mg, subcutaneously [sc], twice daily on days 0-3) are given together with IL-2 (500 U, intraperitoneally [ip], twice daily on days 1-3) or interferon-γ (4,000 U, ip, twice daily on days 1-3). Given the important role of Ia expression in cell-mediated immune reactions, the effect of TGF-β on contact sensitivity was next investigated. In doses of 5 μg, ip, daily on days 6-8, TGF-β inhibits the expression of contact reactivity in animals sensitized on day 0 and challenged on day 7. In contrast, no effect is observed on the induction of contact sensitivity in mice given TGF-β1 on days -1 to 2, sensitized on day 0, and challenged on day 7. The possible importance of antagonism between TGF-β and other cytokines, especially IFN-γ, involved in the elicitation of contact hypersensitivity reactions is discussed.

Original languageEnglish
Pages (from-to)832-837
Number of pages6
JournalJournal of Investigative Dermatology
Volume96
Issue number6
DOIs
StatePublished - Jun 1990
Externally publishedYes

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