Subsets of human CD4(+) regulatory T cells express the peripheral homing receptor CXCR3.
Eur J Immunol
; 41(8): 2291-302, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21538345
ABSTRACT
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 â¼30-40% 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-γ 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-γ-inducible protein of 10 kDa (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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Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
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Linfócitos T Reguladores
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Fatores de Transcrição Forkhead
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Receptores CXCR3
Limite:
Adult
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Child
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article