RelA regulates the survival of activated effector CD8 T cells.
Nuclear factor of kappa B (NF-kappaB) transcription factors are critical regulators of T-cell activation and survival. The relative contribution of individual NF-kappaB members to these processes remains elusive. We investigated the role of RelA in the regulation of CD8 T-cell activation. We overexpressed, in mature CD8 T cells, a transactivation domain-deficient RelA molecule (p65TAD). We show that p65TAD forms homo- and heterodimers with p50 that bind kappaB sites and selectively inhibit RelA-dependent transactivation. Expression of p65TAD does not affect initial activation or cell cycle progression but induces the death of activated CD8 T cells in vitro and in vivo. However, the long-term survival of resting effector CD8 T cells seems not to be affected by p65TAD expression. Collectively, our results indicate that RelA is a critical regulator of survival of proliferating CD8 T cells but may be dispensable for the survival of resting effector T cells.
Mondor
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I
Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique/Université de la Méditerranée, Parc Scientifique de Luminy, Marseille, France.
Schmitt-Verhulst
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AM
Guerder
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S
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001665:Binding Sites; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D048708:Cell Growth Processes; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation
C498143:RELA protein, human; D051996:Transcription Factor RelA