MHC CLASS-II MOLECULES REGULATE GROWTH IN HUMAN T-CELLS

MHC-class-II-positive T cells are found in tissues involved in autoimm une disorders. Stimulation of class II molecules by monoclonal antibod ies (mAbs) or bacterial superantigens induces protein tyrosine phospho rylation through activation of protein tyrosine kinases in T cells, an d class II signals modulate several T cell responses. Here, we studied further the role of class II molecules in the regulation of T cell gr owth. Costimulation of class II molecules by immobilized HLA-DR mAb si gnificantly enhanced interleukin (IL)-2-supported T cell growth of the majority of CD4+, CD45RA(low), RO(high) T cell lines tested. Only one of three CD4+, CD45RA(high), RO(high) T cells responded to class II c ostimulation. There was no correlation between T cell responsiveness t o class II and the cytokine production profile of the T cell in questi on. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 ( T-H1-like) as well as T cells producing both cytokines (T-HO-like) res ponded to class II mAb. The costimulatory effect was not restricted to IL-2-driven T cell growth, since TCR/CD3-induced T cell activation wa s also enhanced by HLA-DR mAb. Moreover, class II costimulation potent iated CD28-mAb-induced T cell sensitivity to protein kinase C activati on by phorbol 12-myristate 13-acetate. In conclusion, class II costimu lation enhances T cell activation through the TCR/CD3 and IL-2 pathway s and interacts with CD28 accessory signals to up-regulate growth of a llospecific T cell lines.