Cutting edge: Regulatory T cells selectively attenuate, not terminate, T cell signaling by disrupting NF-κB nuclear accumulation in CD4 T cells.
A key consequence of regulatory T cell (Treg) suppression of CD4 T cells is the inhibition of IL-2 production, yet how Tregs attenuate IL-2 has not been defined. Current models predict a termination of TCR signaling, by disrupting T-APC contacts, or TCR signal modification, through mechanisms such as cAMP. To directly define Treg effects on TCR signaling in CD4 T cell targets, we visualized changes in nuclear accumulation of transcription factors at time points when IL-2 was actively suppressed. Nuclear accumulation of NFAT was highly dependent on sustained TCR signaling in the targets. However, in the presence of Tregs, NFAT and AP-1 signals were sustained in the target cells. In contrast, NF-κB p65 was selectively attenuated. Thus, Tregs do not generally terminate TCR signals. Rather, Tregs selectively modulate TCR signals within hours of contact with CD4 targets, independent of APCs, resulting in the specific loss of NF-κB p65 signals.
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester, Rochester, NY 14642, USA.
Yu-Hui
YH
Huang
Dorothy K
DK
Sojka
Deborah J
DJ
Fowell
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D007376:Interleukin-2; D050778:NFATC Transcription Factors; C498144:Rela protein, mouse; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D014157:Transcription Factors