title: 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 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.
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garner's Ferry Road, Columbia, SC 29209, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Melencio
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McKallip
authors.forename: Hongbing
authors.initials: H
authors.lastname: Guan
authors.forename: Rupal
authors.initials: R
authors.lastname: Ramakrishnan
authors.forename: Reena
authors.initials: R
authors.lastname: Jain
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Nagarkatti
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
mesh_terms: 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
chemical_list: D007376:Interleukin-2