Depletion of CD4+ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques
Alexandra M. Ortiz, … , Cynthia A. Derdeyn, Guido Silvestri
Alexandra M. Ortiz, … , Cynthia A. Derdeyn, Guido Silvestri
Published October 17, 2011
Citation Information: J Clin Invest. 2011;121(11):4433-4445. https://doi.org/10.1172/JCI46023.
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Research Article AIDS/HIV

Depletion of CD4+ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques

Abstract

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.

Authors

Alexandra M. Ortiz, Nichole R. Klatt, Bing Li, Yanjie Yi, Brian Tabb, Xing Pei Hao, Lawrence Sternberg, Benton Lawson, Paul M. Carnathan, Elizabeth M. Cramer, Jessica C. Engram, Dawn M. Little, Elena Ryzhova, Francisco Gonzalez-Scarano, Mirko Paiardini, Aftab A. Ansari, Sarah Ratcliffe, James G. Else, Jason M. Brenchley, Ronald G. Collman, Jacob D. Estes, Cynthia A. Derdeyn, Guido Silvestri

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Figure 4

SIV infection induces systemic CD4+ T cell loss in both groups of CD4+ lymphocyte–depleted and undepleted RMs.

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SIV infection induces systemic CD4+ T cell loss in both groups of CD4+ l...
Longitudinal assessment of CD4+ T cell levels after SIV infection. (A) Circulating CD4+ T cells, shown as percent relative to baseline (pre-SIV infection), percent of CD3+ T cells, and absolute CD4+ T cell count per μl, in CD4+ lymphocyte–depleted and control RMs and RUv6. (B) Longitudinal assessment of CD4+ T cells (measured as percent of baseline) in the BM, LN, and RB. (C) Longitudinal assessment of CD4+ T cells (measured as percent of CD3+ T cells).