Subsets of memory cytotoxic T lymphocytes elicited by vaccination influence the efficiency of secondary expansion in vivo

J Virol. 2004 Jan;78(1):206-15. doi: 10.1128/jvi.78.1.206-215.2004.

Abstract

Vaccine-elicited cytotoxic T lymphocytes (CTL) should be long-lived memory cells that can rapidly expand in number following re-exposure to antigen. The present studies were initiated to analyze the ability of plasmid interleukin-12 (IL-12) to augment CTL responses in mice when delivered during the peak phase of an immune response elicited by a plasmid human immunodeficiency virus type 1 gp120 DNA vaccine. Delivery of plasmid IL-12 on day 10 postimmunization resulted in a robust expansion of gp120-specific CD8+ T cells, as measured by tetramer, gamma interferon ELISPOT, and functional-killing assays. Interestingly, this delayed administration of plasmid IL-12 had no significant effect on antigen-specific CD4(+)-T-cell and antibody responses. Phenotypic analyses suggested that administration of plasmid IL-12 near the time of the peak CTL response activated and expanded antigen-specific effector cells, preventing their loss through apoptosis. However, this IL-12-augmented population of gp120-specific CD8+ T cells did not efficiently expand following gp120 boost immunization, suggesting that these effector cells would be of little utility in expanding to contain a viral infection. Analyses of the phenotypic profile and anatomic distribution of the plasmid IL-12-augmented CTL population indicated that these lymphocytes were primarily effector memory rather than central memory T cells. These observations suggest that CTL-based vaccines should elicit central memory rather than effector memory T cells and illustrate the importance of monitoring the phenotype and functionality of vaccine-induced, antigen-specific CTL.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Animals
  • Cytotoxicity Tests, Immunologic
  • Female
  • HIV Envelope Protein gp120 / administration & dosage
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology
  • Humans
  • Immunization, Secondary
  • Immunologic Memory*
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology*
  • Lymphocyte Activation / immunology*
  • Mice
  • Plasmids
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Vaccination
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology

Substances

  • AIDS Vaccines
  • HIV Envelope Protein gp120
  • Vaccines, DNA
  • Interleukin-12