Selective activation of resting human γδ T lymphocytes by interleukin‐2

Abstract

In rheumatoid arthritis and other inflammatory diseases we and others have found that gamma delta 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 gamma delta T cells. Short-term exposure (24-96 h) to rIL-2 selectively stimulated the gamma delta but not the alpha beta 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 gamma delta T cells and a corresponding reduction of the fraction of alpha beta T cells. Limiting dilution analysis revealed that approximately 1/60 of the gamma delta T cells responded to IL-2 in contrast to only 1/250 of the alpha beta 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 gamma delta and alpha beta T cells whereas the relative density of the beta chain was more than twice as high on gamma delta T cells. Both the IL-2-induced proliferation of gamma delta T cells and the expression of activation antigens on these cells could be inhibited by an anti-IL-2R beta monoclonal antibody (mAb) but not by an anti-IL-2R alpha mAb. Expression of CD69 on gamma delta T cells was dependent neither on the presence of B cells, monocytes, nor alpha beta 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 gamma delta 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 gamma delta T cells in inflammatory diseases is an epiphenomenon secondary to IL-2 produced by activated alpha beta T cells.

Drug-Induced Expansion and Differentiation of Vγ9Vδ2 T Cells In Vivo: The Role of Exogenous IL-2

“…Moreover, only ␥␦, but not ␣␤, T cells were expressing the CD69 activation marker shortly after the IL-2 treatment, suggesting that ␥␦ T lymphocytes may be more sensitive to low doses of s.c. IL-2 than ␣␤ T cells. This is compatible with the finding that short-term exposures to IL-2 in vitro induce the expression of CD69, CD25, and HLA-DR on human ␥␦, but not ␣␤, T cells (36). Comparable amounts of the IL-2R␣-chain are expressed on ␥␦ and ␣␤ T cells, whereas the relative density of the IL-2R␤-chain is more than twice as high on ␥␦ cells, a feature which they share with NK cells.…”

Expression and regulation of adhesion molecules by γδ T cells from lymphoid tissues and intestinal epithelium

“…These findings are consistent with y6 T cells in normal mice having previously responded to foreign environmental antigens. In addition, the ability of IL-2 to activate y6 cells in the absence of stimulation by antigen would explain the excess of y6 cells with an activated phenotype [52]. The differential expression of adhesion molecules on V64+ vs. V64-cells (Fig.…”

Circulating V?1 + T cells are activated and accumulate in the skin of systemic sclerosis patients

“…In our patients, the Val+ subset expressed HLA-DR without coexpressing CD45R0, presumably representing unprimed y/S T cells or, alternatively, y/S T cells which do not need to be triggered via the TCR in order to express both activation and "memory" markers. In fact, shortterm culture with recombinant interleukin-2 induces a significant expression of "memory" markers on y/S T cells, but not on alp T cells (38), suggesting that this expression could be induced by interleukins (39), which are produced in large amounts by other cells in patients with SSc (40).…”