期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 41, 期 8, 页码 2291-2302出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201041095
关键词
Chemokine receptors; Chemokines; CXCR3; Immunoregulation; Tregs
类别
资金
- National Institutes of Health [U01 AI46135, PO1 AI50157, R01 GM092804]
- Deutsche Forschungsgemeinschaft [HO2581/3-1]
- Damon Runyon Cancer Research Foundation
- National Institute of Allergy and Infectious Diseases, National Institutes of Health
Regulatory T cells (Tregs) migrate into peripheral sites of inflammation such as allografts undergoing rejection, where they serve to suppress the immune response. In this study, we find that similar to 30-40% of human CD25(hi) FOXP3(+) CD4(+) Tregs express the peripheral CXC chemokine receptor 3 (CXCR3) and that this subset has potent immunoregulatory properties. Consistently, we observed that proliferative responses as well as IFN-gamma production were significantly higher using CXCR3-depleted versus undepleted responders in the mixed lymphocyte reaction, as well as following mitogen-dependent activation of T cells. Using microfluidics, we also found that CXCR3 was functional on CXCR3(pos) Tregs, in as much as chemotaxis and directional persistence towards interferon-gamma-inducible protein of 10kDa (IP-10) was significantly greater for CXCR3(pos) than CXCR3(neg) Tregs. Following activation, CXCR3-expressing CD4(+) Tregs were maintained in vitro in cell culture in the presence of the mammalian target of rapamycin (mTOR) inhibitor rapamycin, and we detected higher numbers of circulating CXCR3(+) FOXP3(+) T cells in adult and pediatric recipients of renal transplants who were treated with mTOR-inhibitor immunosuppressive therapy. Collectively, these results demonstrate that the peripheral homing receptor CXCR3 is expressed on subset(s) of circulating human Tregs and suggest a role for CXCR3 in their recruitment into peripheral sites of inflammation.
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