IFN-γ regulates CD8(+) memory T cell differentiation and survival in response to weak, but not strong, TCR signals

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Item Type:	Article
Title:	IFN-γ regulates CD8(+) memory T cell differentiation and survival in response to weak, but not strong, TCR signals
Creators Name:	Stoycheva, D., Deiser, K., Stärck, L., Nishanth, G., Schlüter, D., Uckert, W. and Schüler, T.
Abstract:	In response to primary Ag contact, naive mouse CD8+ T cells undergo clonal expansion and differentiate into effector T cells. After pathogen clearance, most effector T cells die, and only a small number of memory T cell precursors (TMPs) survive to form a pool of long-lived memory T cells (TMs). Although high- and low-affinity CD8+ T cell clones are recruited into the primary response, the TM pool consists mainly of high-affinity clones. It remains unclear whether the more efficient expansion of high-affinity clones and/or cell-intrinsic processes exclude low-affinity T cells from the TM pool. In this article, we show that the lack of IFN-gammaR signaling in CD8+ T cells promotes TM formation in response to weak, but not strong, TCR agonists. The IFN-gamma-sensitive accumulation of TMs correlates with reduced mammalian target of rapamycin activation and the accumulation of long-lived CD62LhiBcl-2hiEomeshi TMPs. Reconstitution of mammalian target of rapamycin or IFN-gammaR signaling is sufficient to block this process. Hence, our data suggest that IFN-gammaR signaling actively blocks the formation of TMPs responding to weak TCR agonists, thereby promoting the accumulation of high-affinity T cells finally dominating the TM pool.
Keywords:	Antigen T-Cell Receptors, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Survival, Immunologic Memory, Interferon-gamma, Interferon Receptors, L-Selectin, Knockout Mice, Proto-Oncogene Proteins c-bcl-2, Signal Transduction, T-Box Domain Proteins, TOR Serine-Threonine Kinases, Animals, Mice
Source:	Journal of Immunology
ISSN:	0022-1767
Publisher:	American Association of Immunologists
Volume:	194
Number:	2
Page Range:	553-559
Date:	15 January 2015
Official Publication:	https://doi.org/10.4049/jimmunol.1402058
PubMed:	View item in PubMed

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