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

Journal of Clinical Investigation, ISSN: 0021-9738, Vol: 113, Issue: 6, Page: 836-845
2004
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Article Description

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.

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