Role of CD4(+)CD25(+) T regulatory cells in IL-2-induced vascular leak.
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 T(h)1/T(h)2 bias in IL-2-mediated EC injury using the well-characterized C57BL/6 (T(h)1-biased) and BALB/c (T(h)2-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.
Melencio
Louise
L
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garner's Ferry Road, Columbia, SC 29209, USA.
McKallip
Robert J
RJ
Guan
Hongbing
H
Ramakrishnan
Rupal
R
Jain
Reena
R
Nagarkatti
Prakash S
PS
Nagarkatti
Mitzi
M
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D002199:Capillary Permeability / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013045:Species Specificity; D013577:Syndrome; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D014652:Vascular Diseases / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D007376:Interleukin-2