Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation

Karl S. Lang, Mike Recher, Alexander A. Navarini, Nicola L. Harris, Max Löhning, Tobias Junt, Hans Christian Probst, Hans Hengartner, Rolf M. Zinkernagel

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134 Citations (Scopus)

Abstract

Persistence is a hallmark of infection by viruses such as HIV, hepatitis B virus, hepatitis C virus and LCMV. In the case of LCMV, persistence may often be associated with exhaustion of CD8+ T cells. We demonstrate here that persistent antigen suppressed IL-7Rα expression and this correlated with T cell exhaustion and reduced expression of the anti-apoptotic molecule B cell leukemia/lymphoma 2 (Bcl-2). In contrast, exposure to short-lived antigen only temporarily suppressed IL-7Rα expression, failed to induce T cell exhaustion, and primed T cells. Persistent antigen also suppressed IL-7Rα expression on primed T cells and this correlated with exhaustion of a previously stable primed T cell population. These findings suggest that antigen longevity regulates T cell fate.

Original languageEnglish
Pages (from-to)738-745
Number of pages8
JournalEuropean Journal of Immunology
Volume35
Issue number3
DOIs
Publication statusPublished - 1 Mar 2005
Externally publishedYes

Keywords

  • Bcl-2
  • Exhaustion
  • Lymphocytic choriomeningitis virus
  • Persistence
  • Re-emergence

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