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A role for TNF in limiting the duration of CTL effector phase and magnitude of CD8 T cell memory
Author(s) -
Singh Anju,
Suresh M.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0407240
Subject(s) - biology , lymphocytic choriomeningitis , cytotoxic t cell , effector , cd8 , tumor necrosis factor alpha , microbiology and biotechnology , immunology , cytokine , t cell , interleukin 21 , immune system , in vitro , genetics
It is known that TNF‐α (TNF) exerts distinct tissue‐protective or ‐destructive effects in the pathogenesis of T cell‐dependent immunopathology, depending on the context and amount of cytokine produced. To better understand the cellular mechanisms underlying the regulation of T cells by TNF, we have analyzed the role of TNF in regulating various facets of the antigen‐specific CD8 T cell response to lymphocytic choriomeningitis virus (LCMV) in mice. We show that expansion and differentiation of virus‐specific effector CD8 T cells and LCMV clearance are not dependent on TNF. Instead, we demonstrate that TNF limits the duration of the effector phase of the CD8 T cell response by regulating apoptosis and not proliferation of effector cells in vivo. We further show that attenuation of effector cell apoptosis induced by TNF deficiency led to a substantial increase in the number of virus‐specific memory CD8 T cells without affecting their function. The enhancement in the number of memory CD8 T cells in TNF‐deficient (TNF−/−) mice was not associated with up‐regulation of IL‐7Rα or Bcl‐2 in effector cells, which indicated that TNF might limit differentiation of memory cells from IL‐7R lo effector cells. Collectively, these data are strongly suggestive of a role for TNF in down‐regulating CD8 T cell responses and the establishment of CD8 T cell memory during an acute viral infection. These findings further our understanding of the regulation of CD8 T cell homeostasis and have implications in vaccine development and clinical use of anti‐TNF therapies to treat T cell‐dependent, inflammatory disorders.