期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 121, 期 11, 页码 4433-4445出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI46023
关键词
-
资金
- NIH [AI-66998, RR-00165]
- National Cancer Institute, NIH [HHSN261200800001E]
CD4(+) T cells play a central role in the immunopathogenesis of HIV/AIDS, and their depletion during chronic HIV infection is a hallmark of disease progression. However, the relative contribution of CD4(+) T cells as mediators of antiviral immune responses and targets for virus replication is still unclear. Here, we have generated data in SW-infected rhesus macaques (RMs) that suggest that CD4(+) T cells are essential in establishing control of virus replication during acute infection. To directly assess the role of CD4(+) T cells during primary SW infection, we in vivo depleted these cells from RMs prior to infecting the primates with a pathogenic strain of SIV. Compared with undepleted animals, CD4(+) lymphocyte-depleted RMs showed a similar peak of viremia, but did not manifest any post-peak decline of virus replication despite CD8(+) T cell- and B cell-mediated SW-specific immune responses comparable to those observed in control animals. Interestingly, depleted animals displayed rapid disease progression, which was associated with increased virus replication in non-T cells as well as the emergence of CD4-independent SW-envelopes. Our results suggest that the antiviral CD4(+) T cell response may play an important role in limiting SW replication, which has implications for the design of HIV vaccines.
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