A regulatory role for CD37 in T cell proliferation.
CD37 is a leukocyte-specific protein belonging to the tetraspanin superfamily. Previously thought to be predominantly a B cell molecule, CD37 is shown in this study to regulate T cell proliferation. CD37-deficient (CD37(-/-)) T cells were notably hyperproliferative in MLR, in response to Con A, or CD3-TCR engagement particularly in the absence of CD28 costimulation. Hyperproliferation was not due to differences in memory to naive T cell ratios in CD37(-/-) mice, apoptosis, or TCR down-modulation. Division cycle analyses revealed CD37(-/-) T cells to enter first division earlier than wild-type T cells. Importantly, proliferation of CD37(-/-) T cells was preceded by enhanced early IL-2 production. We hypothesized CD37 to be involved in TCR signaling and this was supported by the observation that CD4/CD8- associated p56(Lck) kinase activity was increased in CD37(-/-) T cells. Remarkably, CD37 cross- linking on human T cells transduced signals that led to complete inhibition of CD3-induced proliferation. In the presence of CD28 costimulation, CD37 engagement still significantly reduced proliferation. Taken together, these results demonstrate a regulatory role for CD37 in T cell proliferation by influencing early events of TCR signaling.[1]References
- A regulatory role for CD37 in T cell proliferation. van Spriel, A.B., Puls, K.L., Sofi, M., Pouniotis, D., Hochrein, H., Orinska, Z., Knobeloch, K.P., Plebanski, M., Wright, M.D. J. Immunol. (2004) [Pubmed]
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