Expansion of FOXP3+ CD8 T Cells with Suppressive Potential in Colorectal Mucosa Following a Pathogenic Simian Immunodeficiency Virus Infection Correlates with Diminished Antiviral T Cell Response and Viral Control

被引:67
作者
Nigam, Pragati [1 ]
Velu, Vijayakumar [1 ]
Kannanganat, Sunil [1 ]
Chennareddi, Lakshmi [1 ]
Kwa, Suefen [1 ]
Siddiqui, Mariam [1 ]
Amara, Rama Rao [1 ]
机构
[1] Emory Univ, Sch Med, Dept Microbiol & Immunol, Emory Vaccine Ctr,Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA
基金
美国国家卫生研究院;
关键词
GROWTH-FACTOR-BETA; PERIPHERAL-BLOOD; REGULATORY CELLS; SIV INFECTION; IN-VITRO; IMMUNE-RESPONSES; RHESUS MACAQUES; CUTTING EDGE; LYMPH-NODES; CD4(+);
D O I
10.4049/jimmunol.0902955
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
FOXP3(+)CD8(+) T cells are present at low levels in humans; however, the function of these cells is not known. In this study, we demonstrate a rapid expansion of CD25(+)FOXP3(+)CD8(+) regulatory T cells (Tregs) in the blood and multiple tissues following a pathogenic SIV infection in rhesus macaques. The expansion was pronounced in lymphoid and colorectal mucosal tissues, preferential sites of virus replication. These CD8 Tregs expressed molecules associated with immune suppressor function such as CTLA-4 and CD39 and suppressed proliferation of SIV-specific T cells in vitro. They also expressed low levels of granzyme B and perforin, suggesting that these cells do not possess killing potential. Expansion of CD8 Tregs correlated directly with acute phase viremia and inversely with the magnitude of antiviral T cell response. Expansion was also observed in HIV-infected humans but not in SIV-infected sooty mangabeys with high viremia, suggesting a direct role for hyperimmune activation and an indirect role for viremia in the induction of these cells. These results suggest an important but previously unappreciated role for CD8 Tregs in suppressing antiviral immunity during immunodeficiency virus infections. These results also suggest that CD8 Tregs expand in pathogenic immunodeficiency virus infections in the nonnatural hosts and that therapeutic strategies that prevent expansion of these cells may enhance control of HIV infection. The Journal of Immunology, 2010, 184: 1690-1701.
引用
收藏
页码:1690 / 1701
页数:12
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