An essential role for TNF in modulating thresholds for survival, activation, and tolerance of CD8+ T cells

Ioannis Chatzidakis, Georgia Fousteri, Debbie Tsoukatou, George Kollias, Clio Mamalaki

Research output: Contribution to journalArticle

Abstract

TNF and its receptors p55 and p75 are known to be important in the homeostasis of the peripheral immune system. Previous studies have presented apparently contradictory evidence for an in vivo role of TNF in T cells. In this study, we analyzed TNF-deficient mice crossed with the F5 TCR-transgenic animals. We show that endogenous TNF modulates several aspects of homeostasis of peripheral F5 CD8 T cells. We found that F5/TNF_/_ mice had reduced numbers of peripheral F5 T cells, F5/TNF-/_ CD8 T cells exhibited reduced survival potential, and furthermore that T cell-derived TNF is required for optimum recovery of naive CD8 T cells in lymphopenic hosts, suggesting its involvement in the survival of peripheral CD8 T cells. Both peptide activation and ensuing Ag-induced apoptosis are quantitatively reduced in TNF-/_ CD8 T cells. The latter observations can be related to decreased binding activities of NF-κB and NF-ATp observed in Ag-stimulated F5/TNF _/- T cells. Finally, in a CD8 T cell tolerance model, endogenous TNF was necessary for several parameters of CD8 T cell tolerance induction. Collectively, our results provide evidence that endogenous TNF modulates thresholds in several ligand-driven T cell responses.

Original languageEnglish
Pages (from-to)6735-6745
Number of pages11
JournalJournal of Immunology
Volume178
Issue number11
Publication statusPublished - Jun 1 2007

ASJC Scopus subject areas

  • Immunology

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    Chatzidakis, I., Fousteri, G., Tsoukatou, D., Kollias, G., & Mamalaki, C. (2007). An essential role for TNF in modulating thresholds for survival, activation, and tolerance of CD8+ T cells. Journal of Immunology, 178(11), 6735-6745.