Immunosuppressive effects of transforming growth factor beta: inhibition of the induction of Ia antigen on Langerhans cells by cytokines and of the contact hypersensitivity response.
Recent reports show that transforming growth factor (TGF)-beta exerts a variety of immunosuppressive activities. The present study focuses on the effects of TGF-beta 1 on expression of Ia antigen by Langerhans cells. Although TGF-beta 1, in concentrations from 0.001 to 100 micrograms/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-alpha, interferon-gamma, IL-3, and granulocyte/macrophage-colony stimulating factor is inhibited by the concomitant addition of 1 microgram/ml TGF-beta 1. In contrast, TGF-beta 1 has no effect on the up-regulation induced by IL-2 or IL-6. In this report, the activity of TGF-beta closely resembles that of Cyclosporine A (CsA). Similar results are seen in vivo when either TGF-beta 1 (5 micrograms, 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-gamma (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-beta on contact sensitivity was next investigated. In doses of 5 micrograms, ip, daily on days 6-8, TGF-beta 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-beta 1 on days--1 to 2, sensitized on day 0, and challenged on day 7. The possible importance of antagonism between TGF-beta and other cytokines, especially IFN-gamma, involved in the elicitation of contact hypersensitivity reactions is discussed.
Epstein
S P
SP
Department of Dermatology, New York University School of Medicine, New York.
Baer
R L
RL
Thorbecke
G J
GJ
Belsito
D V
DV
D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors*; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000502:physiology; D007166:Immunosuppressive Agents; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D010853:Picryl Chloride