期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 41, 期 4, 页码 1058-1069出版社
WILEY
DOI: 10.1002/eji.201041198
关键词
HIV; Immune activation; JAK/STAT; SOCS
类别
资金
- EMDO Foundation
- OPO Foundation
- Hartmann-Muller Foundation
- Swiss National Science Foundation [320030_127618/1]
- Swiss National Science Foundation (SNF) [320030_127618] Funding Source: Swiss National Science Foundation (SNF)
HIV infection is characterized by sustained immune activation, which is reflected by activated T cells and, in particular, by increased levels of phosphorylated STAT proteins. Here, we hypothesized that T-cell activation in HIV infection is partially due to the inability of SOCS-1 and SOCS-3 to control the JAK/STAT pathway. We found higher levels of SOCS-1/3 mRNA levels in CD4(+) T cells of HIV-infected patients than in healthy controls. However, SOCS protein levels were lower, explaining the lack of attenuation of the JAK/STAT pathway. Infection of CD4(+) T cells alone did not activate STATs, while ex vivo infection of PBMC did, indicating that non-T cells critical for shaping the immune response, e. g. DC were responsible for the STAT-1 activation. Supernatants from ex vivo-infected PBMC transferred to CD4(+) T cells induced JAK/STAT activation, pointing to a central role of soluble factors. Notably, over-expression of SOCS-1/3 in CD4(+) T cells prevented JAK/STAT activation. Thus, HIV infection interferes with SOCS-1/3 expression driving immune activation. Sustained immune activation disrupts the lymphoid system and favors HIV replication since HIV preferentially infects activated cells. We speculate that regulating SOCS may be a potential way to counteract immune activation in HIV disease.
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