International Immunology Advance Access originally published online on August 16, 2006
International Immunology 2006 18(10):1461-1471; doi:10.1093/intimm/dxl079
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Role of CD4+CD25+ T regulatory cells in IL-2-induced vascular leak
1 Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garner's Ferry Road, Columbia, SC 29209, USA
2 Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
Correspondence to: M. Nagarkatti; E-mail: mnagark{at}med.sc.edu
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.
Keywords: IL-2, Th1/Th2 cytokine, T regulatory cells, vascular leak
Transmitting editor: L. Glimcher
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