CLTA-4 blockade in vivo promotes the generation of short-lived effector CD8+ T cells and a more persistent central memory CD4+ T cell response

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Abstract

Background

Previously, we examined the effects of in vivo CTLA-4 blockade using a fully human monoclonal antibody as a part of a DNA vaccination regimen in cynomolgus macaques (Macaca fascicularis). We observed that while the antibody had little effect on the IFN-γ ELISpot response, CTLA-4 blockade enhanced antigen-specific cellular proliferation in both CD4+ and CD8+T-cell compartments.

Methods

We examine the specific effects of CTLA-4 blockade on memory T-cell compartments following the third immunization and 10 months following a fourth immunization, during the memory phase of the immune response.

Results

CLTA-4 blockade enhanced CD4+ and CD8+ central memory (CD28hi, CD95hi) T-cell responses as well as a short-lived CD8+ effector (CD28lo, CD95hi) T-cell response.

Conclusions

These data suggest differing effects of CTLA-4 blockade on CD4+ and CD8+ T cells with implications on the clinical use of anti-CTLA-4 antibodies for enhancement of vaccine strategies or treatment of human disease.

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