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

J Med Primatol. 2008 Dec:37 Suppl 2:62-8. doi: 10.1111/j.1600-0684.2008.00324.x.

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-gamma 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 (CD28(hi), CD95(hi)) T-cell responses as well as a short-lived CD8(+) effector (CD28(lo), CD95(hi)) 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • Female
  • Flow Cytometry
  • Immunologic Memory / immunology*
  • Macaca fascicularis
  • Male
  • Models, Immunological
  • Vaccines, DNA / administration & dosage

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Vaccines, DNA