title: 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: Yerkes National Primate Research Center and Emory Vaccine Center, Emory University, Atlanta, Georgia, USA.
authors: Alexandra M
authors: AM
authors: Ortiz
authors: Nichole R
authors: NR
authors: Klatt
authors: Bing
authors: B
authors: Li
authors: Yanjie
authors: Y
authors: Yi
authors: Brian
authors: B
authors: Tabb
authors: Xing Pei
authors: XP
authors: Hao
authors: Lawrence
authors: L
authors: Sternberg
authors: Benton
authors: B
authors: Lawson
authors: Paul M
authors: PM
authors: Carnathan
authors: Elizabeth M
authors: EM
authors: Cramer
authors: Jessica C
authors: JC
authors: Engram
authors: Dawn M
authors: DM
authors: Little
authors: Elena
authors: E
authors: Ryzhova
authors: Francisco
authors: F
authors: Gonzalez-Scarano
authors: Mirko
authors: M
authors: Paiardini
authors: Aftab A
authors: AA
authors: Ansari
authors: Sarah
authors: S
authors: Ratcliffe
authors: James G
authors: JG
authors: Else
authors: Jason M
authors: JM
authors: Brenchley
authors: Ronald G
authors: RG
authors: Collman
authors: Jacob D
authors: JD
authors: Estes
authors: Cynthia A
authors: CA
authors: Derdeyn
authors: Guido
authors: G
authors: Silvestri
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D012367:RNA, Viral / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D019562:Viral Load / Q000276:immunology; D014766:Viremia / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D000961:Antilymphocyte Serum; D015704:CD4 Antigens; D017931:DNA Primers; D012367:RNA, Viral