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Influence of Tumor Necrosis Factor- on the Modulation by Interferon- of HLA Class II Molecules in Human Thyroid Cells and Its Effect on Interferon- Binding^*

MASSIMO BUSCEMA, IAN TODD, ULRICH DEUSS, LINDA HAMMOND, RITA MIRAKIAN, RICARDO PUJOL-BORRELL^¶ and GIAN FRANCO BOTTAZZO

Department of Immunology, University College and Middlesex School of Medicine London, W1P 9PG United Kingdom

Address all correspondence and requests for reprints to: Dr. G. F. Bottazzo, Department of Immunology, University College and Middlesex School of Medicine, Arthur Stanley House, 40-50 Tottenham Street, London, WlP 9PG United Kingdom.

Cytokines are important modulators of immunological reactions, but it has been postulated that they might act on other unrelated epithelial cells. We studied the effects of recombinant interferon- (rIFN) and recombinant tumor necrosis factor- (rTNF) on normal human thyroid cells. We found that the combination of these two cytokines enhanced HLA class II molecule expression on these cells compared with the effect of rIFN alone. This was proven by both immunofluorescence as well as a more sensitive and quantitative RIA. rTNF alone had no effect on HLA class II molecule induction on the same thyrocytes, suggesting a synergistic rather than an additive action in combination with rIFN. The addition of 600 U/ml rTNF to low dose rIFN (10 U/mL) enhanced class II expression by 50%, as quantified by RIA. We also demonstrated that normal thyrocytes possess distinct receptors for the two cytokines and that rTNF probably augments IFN binding, since it increased when the cells were first incubated with rTNF. This increased binding provides an explanation for the synergistic action of rTNF in enhancing class II molecule expression by rlFN. We conclude that the presence of receptors for these cytokines on human thyroid cells gives a direct demonstration of their potential biological action on cells normally not involved in the immunological circuit. The phenomenon might also explain their direct or indirect involvement in vivo, such as in influencing inappropriate HLA class II molecule expression in epithelial cells affected by autoimmunity.

^* This work was supported in part by the Wellcome Trust.

Present address: Cattedra di Endocrinologia, Ospedale Garibaldi, 95124 Catania, Italy. Recipient of a fellowship from the Juvenile Diabetes Foundation.

Present address: Department of Immunology, Queen's Medical Centre, Nottingham, NG7 2UH United Kingdom.

Present address: Med. universitaetsklinik II, Krankenhaus Koeln-Merheim, 5000 Koeln 91, West Germany. Supported by a grant from the Deutsche Forschungsgemeinschaft, West Germany (De 373/1-1).

^¶ Present address: Universidad Autonoma de Barcelona, Department of Medicine, 08916 Barcelona, Spain. Recipient of a Career Development Award from the Juvenile Diabetes Foundation.

Received December 5, 1988.

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