T cell sensitivity to TGF-β is required for the effector function but not the generation of splenic CD8+ regulatory T cells induced via the injection of antigen into the anterior chamber

被引:10
|
作者
Cone, Robert E. [1 ,2 ]
Chattopadhyay, Subhasis [1 ]
Sharafieh, Roshanak [1 ]
Lemire, Yen [1 ]
O'Rourke, James [1 ,2 ]
Flavell, Richard A. [3 ,4 ]
Clark, Robert B. [1 ,5 ,6 ]
机构
[1] Univ Connecticut, Ctr Hlth, Dept Immunol, Farmington, CT 06030 USA
[2] Univ Connecticut, Ctr Hlth, Connecticut Lions Vasc Vis Ctr, Farmington, CT 06030 USA
[3] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
[4] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA
[5] Univ Connecticut, Ctr Hlth, Ctr Immunotherapy Canc & Infect Dis, Farmington, CT 06030 USA
[6] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT 06030 USA
基金
美国国家卫生研究院;
关键词
regulatory T cell; TGF-beta; tolerance; suppression; IMMUNE DEVIATION ACAID; DELAYED-TYPE HYPERSENSITIVITY; GROWTH-FACTOR-BETA; IN-VITRO; CBL-B; ALLOGRAFT-REJECTION; SUPPRESSOR-CELLS; INTERFERON-GAMMA; CUTTING EDGE; MICE;
D O I
10.1093/intimm/dxp023
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The introduction of antigen into the anterior chamber (AC) of the eye induces the production of antigen-specific splenic CD8(+) regulatory T cells (AC-SPL cells) that suppress a delayed-type hypersensitivity (DTH) reaction in immunized mice. Because the generation of these regulatory T cells is also induced by exposure to transforming growth factor (TGF)-beta and antigen or F4/80(+) cells exposed to TGF-beta and antigen in vitro, we investigated (i) whether these cells are produced in dominant negative receptor for transforming growth factor beta receptor type II (dnTGF beta RII) or Cbl-b(-/-) mice whose T cells are resistant to TGF-beta, (ii) whether DTH is suppressed by wild type (WT) CD8(+) AC-SPL cells in Cbl-b(-/-) and dnTGF beta RII mice and (iii) the effect of antibodies to TGF-beta on the suppression of DTH by CD8(+) AC-SPL cells. DnTGF beta RII immunized and Cbl-b(-/-) mice produced splenic CD8(+) regulatory cells after the intracameral injection of antigen and immunization. The suppression of a DTH reaction by CD8(+) AC-SPL cells in WT mice was blocked by the local inclusion of antibodies to TGF-beta when WT splenic CD8(+) AC-SPL cells were injected into the DTH reaction site. Moreover, the DTH reaction in immunized dnTGF beta RII and Cbl-b(-/-) mice was not suppressed by the transfer of WT CD8(+) AC-SPL cells to the site challenged with antigen. In aggregate, these observations suggest that T cell sensitivity to TGF-beta is not an obligate requirement for the in vivo induction of CD8(+) AC-SPL T cells but the suppression of an in vivo DTH reaction by CD8(+) AC-SPL cells is dependent on TGF-beta.
引用
收藏
页码:567 / 574
页数:8
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