Emergence of simian immunodeficiency virus-specific cytotoxic CD4+ T cells and increased humoral responses correlate with control of rebounding viremia in CD8-depleted macaques infected with Rev-independent live-attenuated simian immunodeficiency virus.

Published

Journal Article

Indian rhesus macaques infected with the Rev-independent live-attenuated SIVmac239 strains control viremia to undetectable levels, have persistent but low cellular and humoral anti-SIV responses, and show no signs of immune deficiency. To analyze the immune mechanisms responsible for viral control, five macaques infected at day 1 after birth were subjected to CD8(+) cell depletion at 6.7 y postinfection. This resulted in viremia increases to 3.7-5.5 log(10) RNA copies, supporting a role of CD8-mediated responses in the control of viral replication. The rebounding viremia was rapidly controlled to levels below the threshold of detection, and occurred in the absence of SIV-specific CD8(+) T cells and significant CD8(+) T cell recovery in four of the five animals, suggesting that other mechanisms are involved in the immunological control of viremia. Monitoring immune responses at the time of viral control demonstrated a burst of circulating SIV-specific CD4(+) T cells characterized as CD45RA(-)CD28(+)CD95(+)CCR7(-) and also granzyme B(+), suggesting cytotoxic ability. Control of viremia was also concomitant with increases in humoral responses to Gag and Env, including a transient increase in neutralizing Abs against the neutralization-resistant SIVmac239 in four of five animals. These data demonstrate that a combination of cellular responses mediated by CD4(+) T cells and humoral responses was associated with the rapid control of the rebounding viremia in macaques infected by the Rev-independent live-attenuated SIV, even in the absence of measurable SIV-specific CD8(+) T cells in the blood, emphasizing the importance of different components of the immune response for full control of SIV infection.

Full Text

Duke Authors

Cited Authors

  • von Gegerfelt, A; Valentin, A; Alicea, C; Van Rompay, KKA; Marthas, ML; Montefiori, DC; Pavlakis, GN; Felber, BK

Published Date

  • September 15, 2010

Published In

Volume / Issue

  • 185 / 6

Start / End Page

  • 3348 - 3358

PubMed ID

  • 20702730

Pubmed Central ID

  • 20702730

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1000572

Language

  • eng

Conference Location

  • United States