SELECTIVE ACTIVATION OF RESTING HUMAN-GAMMA-DELTA T-LYMPHOCYTES BY INTERLEUKIN-2

In rheumatoid arthritis and other inflammatory diseases we and others have found that gammadelta T cells express activation antigens, suggesting that they are involved in the pathogenesis of these disorders. In this study we have stimulated peripheral blood mononuclear cells from normal donors with recombinant interleukin-2 (rIL-2) to see whether such a stimulus alone could activate gammadelta T cells. Short-term exposure (24-96 h) to rIL-2 selectively stimulated the gammadelta but not the alphabeta T cells to express activation antigens (CD69, CD25 and HLA-DR). Long-term culture (2 weeks) in rIL-2-containing medium caused a selective increase in the proportion of the gammadelta T cells and a corresponding reduction of the fraction of alphabeta T cells. Limiting dilution analysis revealed that approximately 1/60 of the gammadelta T cells responded to IL-2 in contrast to only 1/250 of the alphabeta T cells. Comparison of the expression of the IL-2 receptor (IL-2R) alpha and beta chains showed that there was a similar expression of the alpha chain on gammadelta and alphabeta T cells whereas the relative density of the beta chain was more than twice as high on gammadelta T cells. Both the IL-2-induced proliferation of gammadelta T cells and the expression of activation antigens on these cells could be inhibited by an anti-IL-2Rbeta monoclonal antibody (mAb) but not by an anti-IL-2Ralpha mAb. Expression of CD69 on gammadelta T cells was dependent neither on the presence of B cells, monocytes, nor alphabeta T cells. Finally, we found that the IL-2-induced expression of CD69 was inhibited by activation of cAMP-dependent protein kinase and by inhibition of the Src-family of the tyrosine protein kinase, but not by inhibition of protein kinase C or by activation of the CD45 associated tyrosine phosphatase. The ability of gammadelta T cells to be activated by IL-2 is a feature which they have in common with natural killer cells. Moreover, it may be possible that the expression of activation antigens on gammadelta T cells in inflammatory diseases is an epiphenomenon secondary to IL-2 produced by activated alphabeta T cells.