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International Immunology Advance Access published online on August 16, 2006
International Immunology, doi:10.1093/intimm/dxl079
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received February 9, 2006
Accepted July 18, 2006

Article

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

Louise Melencio 1, Robert J. McKallip 1, Hongbing Guan 1, Rupal Ramakrishnan 1, Reena Jain 2, Prakash S. Nagarkatti 1, and Mitzi Nagarkatti 1 *

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

* To whom correspondence should be addressed.
Mitzi Nagarkatti, E-mail: mnagark{at}med.sc.edu


  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.

Keywords: IL-2; Th1/Th2 cytokine; T regulatory cells; vascular leak.
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