Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication.


Journal Article

In vivo blockade of CD28 and CD40 T cell costimulation pathways during acute simian immunodeficiency virus (SIV) infection of rhesus macaques was performed to assess the relative contributions of CD4+ T cells, CD8+ T cells, and Ab responses in modulating SIV replication and disease progression. Transient administration of CTLA4-Ig and anti-CD40L mAb to SIV-infected rhesus macaques resulted in dramatic inhibition of the generation of both SIV-specific cellular and humoral immune responses. Acute levels of proliferating CD8+ T cells were associated with early control of SIV viremia but did not predict ensuing set point viremia or survival. The level of in vivo CD4+ T cell proliferation during acute SIV infection correlated with concomitant peak levels of SIV plasma viremia, whereas measures of in vivo CD4+ T cell proliferation that extended into chronic infection correlated with lower SIV viral load and increased survival. These results suggest that proliferating CD4+ T cells function both as sources of virus production and as antiviral effectors and that increased levels of CD4+ T cell proliferation during SIV infections reflect antigen-driven antiviral responses rather than a compensatory homeostatic response. These results highlight the interrelated actions of CD4+ and CD8+ T cell responses in vivo that modulate SIV replication and pathogenesis.

Full Text

Cited Authors

  • Garber, DA; Silvestri, G; Barry, AP; Fedanov, A; Kozyr, N; McClure, H; Montefiori, DC; Larsen, CP; Altman, JD; Staprans, SI; Feinberg, MB

Published Date

  • March 2004

Published In

Volume / Issue

  • 113 / 6

Start / End Page

  • 836 - 845

PubMed ID

  • 15067316

Pubmed Central ID

  • 15067316

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI19442


  • eng

Conference Location

  • United States