Persistent depots of influenza antigen fail to induce a cytotoxic CD8 T cell response

J Immunol. 2007 Jun 15;178(12):7563-70. doi: 10.4049/jimmunol.178.12.7563.

Abstract

Encounter with Ag during chronic infections results in the generation of phenotypically and functionally heterogeneous subsets of Ag-specific CD8 T cells. Influenza, an acute infection, results in the generation of similar CD8 T cell heterogeneity, which may be attributed to long-lived depots of flu Ags that stimulate T cell proliferation well after virus clearance. We hypothesized that the heterogeneity of flu-specific CD8 T cells and maintenance of T cell memory required the recruitment of new CD8 T cells to persistent depots of flu Ag, as was the case for flu-specific CD4 T cell responses. However, robust expansion and generation of highly differentiated cytolytic effectors and memory T cells only occurred when naive CD8 T cells were primed during the first week of flu infection. Priming of new naive CD8 T cells after the first week of infection resulted in low numbers of poorly functional effectors, with little to no cytolytic activity, and a negligible contribution to the memory pool. Therefore, although the presentation of flu Ag during the late stages of infection may provide a mechanism for maintaining an activated population of CD8 T cells in the lung, few latecomer CD8 T cells are recruited into the functional memory T cell pool.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Viral / immunology*
  • Humans
  • Influenza, Human / immunology*
  • Lung / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Viral
  • Receptors, Antigen, T-Cell