Depletion of CD4+ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques
| Autor: | Elena V. Ryzhova, Yanjie Yi, James G. Else, Lawrence R. Sternberg, Ronald G. Collman, Alexandra M. Ortiz, Bing Li, Paul M. Carnathan, Brian Tabb, Sarah J. Ratcliffe, Jessica C. Engram, Xing Pei Hao, Francisco Gonzalez-Scarano, Elizabeth M. Cramer, Nichole R. Klatt, Benton Lawson, Jason M. Brenchley, Dawn M. Little, Mirko Paiardini, Aftab A Ansari, Jacob D. Estes, Cynthia A. Derdeyn, Guido Silvestri |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
viruses T cell Simian Acquired Immunodeficiency Syndrome Viremia Biology Virus Replication medicine.disease_cause Lymphocyte Depletion Immune system In vivo medicine Animals Antilymphocyte Serum DNA Primers Base Sequence virus diseases General Medicine Viral Load Simian immunodeficiency virus medicine.disease Macaca mulatta Virology medicine.anatomical_structure Viral replication CD4 Antigens Immunology RNA Viral Simian Immunodeficiency Virus Viral load CD8 Research Article |
| Zdroj: | Journal of Clinical Investigation. 121:4433-4445 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci46023 |
| Popis: | 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 SIV-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 SIV 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 SIV-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 SIV-envelopes. Our results suggest that the antiviral CD4+ T cell response may play an important role in limiting SIV replication, which has implications for the design of HIV vaccines. |
| Databáze: | OpenAIRE |
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