期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 39, 期 6, 页码 1544-1551出版社
WILEY
DOI: 10.1002/eji.200838603
关键词
Co-stimulation; CTLA-4; Cytokines; Suppression; Treg
类别
资金
- NIH [R01-AI070826, U19 AI056390, T32-A107285]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI070826, U19AI056390] Funding Source: NIH RePORTER
CTLA-4 is constitutively expressed by CD4(+)CD25(+)Foxp3(+) Treg but its precise role in Treg function is not clear. Although blockade of CTLA-4 interferes with Treg function, studies using CTLA-4-deficient Treg have failed to reveal an essential requirement for CTLA-4 in Treg suppression in vivo. Conditional deletion of CTLA-4 in Foxp3(+) T cells disrupts immune homeostasis in vivo but the immune processes disrupted by CTLA-4 deletion have not been determined. We demonstrate that Treg expression of CTLA-4 is essential for Treg control of lymphopenia-induced CD4 T-cell expansion. Despite IL-10 expression, CTLA-4-deficient Treg were unable to control the expansion of CD4(+) target cells in a lymphopenic environment. Moreover, unlike their WT counterparts, CTLA-4-deficient Treg failed to inhibit cytokine production associated with homeostatic expansion and were unable to prevent colitis. Thus, while Treg developing in the absence of CTLA-4 appear to acquire some compensatory suppressive mechanisms in vitro, we identify a non-redundant role for CTLA-4 in Treg function in vivo.
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