Role of CD4+CD25+ T regulatory cells in IL-2-induced vascular leak

Abstract

T regulatory cells (CD4+CD25+) play an important role in the regulation of the immune response. However, little is known about the ability of T regulatory cells to regulate endothelial cell (EC) damage following activation of lymphocytes with IL-2. Therefore, in the current study, we examined the role of T regulatory cells and the subsequent Th1/Th2 bias in IL-2-mediated EC injury using the well-characterized C57BL/6 (Th1-biased) and BALB/c (Th2-biased) models. Following IL-2 treatment, BALB/c mice were less susceptible to IL-2-induced vascular leak syndrome (VLS) compared with C57BL/6 mice. Splenocytes from BALB/c mice displayed less cytotoxicity against ECs compared with those from C57BL/6 mice. Interestingly, BALB/c mice had significantly higher numbers of CD4+CD25+ T regulatory cells, which proliferated more profoundly following IL-2 treatment, compared with CD4+ CD25+ T regulatory cells from C57BL/6 mice. In addition, T regulatory cells from naive BALB/c mice were more potent suppressors of anti-CD3 mAb-stimulated proliferation of T cells than similar cells from C57BL/6 mice. Depletion of T regulatory cells in both BALB/c and C57BL/6 mice led to a significant increase in IL-2-induced VLS. Together, the results from this study suggest that CD4+CD25+ T regulatory cells play an important role in the regulation of IL-2-induced EC injury. © 2006 Oxford University Press.