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The Journal of Immunology, Vol 157, Issue 2 566-573, Copyright © 1996 by American Association of Immunologists


ARTICLES

Th1 development of naive CD4+ T cells is inhibited by co-activation with anti-CD4 monoclonal antibodies

S Goedert, T Germann, P Hoehn, S Koelsch, N Palm, E Rude and E Schmitt
Institute for Immunology, Johannes Gutenberg University, Mainz, Germany.

Co-activation of CD4+ T cells by anti-CD4 mAb strongly enhances the proliferation of these T cells. We have analyzed the influence of CD4- mediated co-activation on Th cell differentiation. Our data demonstrate that activation of high density (HD)-CD4+ T cells by immobilized anti- CD3 mAb in combination with immobilized anti-CD4 mAb led to a strong inhibition of Th1 differentiation and to a variable but significant induction of Th2 development. Priming of highly enriched Mel-14highCD4+ T cells in the presence of anti-CD4 mAb also resulted in a pronounced suppression of secondary IFN-gamma production, indicating that the Th1 development of naive CD4+ T cells is inhibited by co-activation via CD4. In contrast to HD-CD4+ T cells, CD4-induced costimulation of MEL- 14highCD4+ T cells did not result in a primary and secondary IL-4 production. Hence, these results suggest that a MEL-14low population within the HD-CD4+ T cell fraction was the source of the endogenous IL- 4 and imply, in addition, that co-activation via CD4 inhibits the development of Th1 cells from naive CD4+ T cells independently from endogenous IL-4. This assumption is further corroborated by the fact that neither the application of neutralizing anti-IL-4 mAb nor the use of T cells from IL-4 knockout mice could prevent CD4-mediated inhibition of Th1 development. The Th1-inhibiting effect of anti-CD4 mAb could not be reversed by the application of the Th1 inducer IL-12. On the contrary, the secondary IL-4 production of HD-CD4+ T cells as an indicator of Th2 differentiation, which was promoted by anti-CD4 mAb, was enhanced even in the presence of IL-12. Therefore, our results suggest that co-activation of naive CD4+ T cells by anti-CD4 mAb directly and selectively inhibits Th1 differentiation of naive dense CD4+ T cells.


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