Temporal cross‐talk between TCR and STAT signals for CD8 T cell effector differentiation

The strength and duration of signaling through surface receptors is a primary means of controlling cell fate decisions. In adaptive immunity, Ag‐initiated T cell stimulation is secondarily regulated by cytokines. We here summarize evidence for temporal control of a gene expression program in naive C...

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Bibliographic Details
Published in:European Journal of Immunology 2006-12, Vol.36 (12), p.3090-3100
Main Authors: Verdeil, Grégory, Chaix, Julie, Schmitt‐Verhulst, Anne‐Marie, Auphan‐Anezin, Nathalie
Format: Article
Language:English
Subjects:
Animals
CD8-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - metabolism
Cell Differentiation
Cell Differentiation - immunology
Cytolytic T cells
Epigenetics
ERK
Humans
Immunology
Life Sciences
MHC
Partial agonist
Receptor Cross-Talk
Receptor Cross-Talk - physiology
Receptors, Antigen, T-Cell
Receptors, Antigen, T-Cell - physiology
Signal Transduction
Signal Transduction - physiology
STAT Transcription Factors
STAT Transcription Factors - physiology
Time Factors
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Summary:The strength and duration of signaling through surface receptors is a primary means of controlling cell fate decisions. In adaptive immunity, Ag‐initiated T cell stimulation is secondarily regulated by cytokines. We here summarize evidence for temporal control of a gene expression program in naive CD8 T cells. It is initiated in response to TCR engagement but relies on secondary signaling from cytokine receptors to be sustained and to allow development of full effector capacity. This mechanism permits cytokine receptor signaling to rescue abortive TCR signaling, such as that induced in response to weak or partial TCR agonists. Indeed, limiting TCR‐initiated signaling on the Ras/ERK pathway may be complemented by STAT activation. Thus, TCR‐ and cytokine‐driven activation of transcription factors and epigenetic modifications may act in concert in a temporally staggered process to establish the functional program of effector CD8 T cells. Based on gene expression profiling, molecular targets whose activation or inactivation may boost or dampen CD8 T cell effectors are also identified. Manipulation of these targets may, respectively, increase anti‐tumor responses or prevent graft‐versus‐host reactions.
ISSN:0014-2980
1521-4141
1365-2567
DOI:10.1002/eji.200636347