| First Author | Singh A | Year | 2007 |
| Journal | J Leukoc Biol | Volume | 82 |
| Issue | 5 | Pages | 1201-11 |
| PubMed ID | 17704295 | Mgi Jnum | J:127180 |
| Mgi Id | MGI:3763300 | Doi | 10.1189/jlb.0407240 |
| Citation | Singh A, et al. (2007) A role for TNF in limiting the duration of CTL effector phase and magnitude of CD8 T cell memory. J Leukoc Biol 82(5):1201-11 |
| abstractText | It is known that TNF-alpha (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-7Ralpha 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. |
