期刊
JOURNAL OF IMMUNOLOGY
卷 193, 期 11, 页码 5576-5583出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1400961
关键词
-
类别
资金
- National Institutes of Health, National Institute of Allergy and Infectious Diseases, Centers for AIDS Research [AI027757]
- National Center for Research Resources [P51 OD011092, P51 OD011104]
- Creative and Novel Ideas in HIV Research Program [P30 A1027763]
- Office of AIDS Research, National Institute of Allergy and Infectious Diseases
- International AIDS Society
- Delaney AIDS Research Enterprise Grant [AI096109]
- Grants-in-Aid for Scientific Research [24390118] Funding Source: KAKEN
The T cell Ig- and mucin domain-containing molecule-3 (Tim-3) negative immune checkpoint receptor demarcates functionally exhausted CD8(+) T cells arising from chronic stimulation in viral infections like HIV. Tim-3 blockade leads to improved antiviral CD8(+) T cell responses in vitro and, therefore, represents a novel intervention strategy to restore T cell function in vivo and protect from disease progression. However, the Tim-3 pathway in the physiologically relevant rhesus macaque SIV model of AIDS remains uncharacterized. We report that Tim-3(+)CD8(+) T cell frequencies are significantly increased in lymph nodes, but not in peripheral blood, in SIV-infected animals. Tim-3(+)PD-1(+)CD8(+) T cells are similarly increased during SIV infection and positively correlate with SIV plasma viremia. Tim-3 expression was found primarily on effector memory CD8(+) T cells in all tissues examined. Tim-3(+)CD8(+) T cells have lower Ki-67 content and minimal cytokine responses to SIV compared with Tim-3(-)CD8(+) T cells. During acute-phase SIV replication, Tim-3 expression peaked on SIV-specific CD8(+) T cells by 2 wk postinfection and then rapidly diminished, irrespective of mutational escape of cognate Ag, suggesting non-TCR-driven mechanisms for Tim-3 expression. Thus, rhesus Tim-3 in SIV infection partially mimics human Tim-3 in HIV infection and may serve as a novel model for targeted studies focused on rejuvenating HIV-specific CD8(+) T cell responses.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据