'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR.
T cell immunity requires the long-term survival of T cells that are capable of recognizing self antigens but are not overtly autoreactive. How this balance is achieved remains incompletely understood. Here we identify a homeostatic mechanism that transcriptionally tailors CD8 coreceptor expression in individual CD8+ T cells to the self-specificity of their clonotypic T cell receptor (TCR). 'Coreceptor tuning' results from interplay between cytokine and TCR signals, such that signals from interleukin 7 and other common gamma-chain cytokines transcriptionally increase CD8 expression and thereby promote TCR engagement of self ligands, whereas TCR signals impair common gamma-chain cytokine signaling and thereby decrease CD8 expression. This dynamic interplay induces individual CD8+ T cells to express CD8 in quantities appropriate for the self-specificity of their TCR, promoting the engagement of self ligands, yet avoiding autoreactivity.
Park
Jung-Hyun
JH
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Adoro
Stanley
S
Lucas
Philip J
PJ
Sarafova
Sophia D
SD
Alag
Amala S
AS
Doan
Loretta L
LL
Erman
Batu
B
Liu
Xiaolong
X
Ellmeier
Wilfried
W
Bosselut
Remy
R
Feigenbaum
Lionel
L
Singer
Alfred
A
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D006706:Homeostasis; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D016827:CD8 Antigens; D016207:Cytokines; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell