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J Immunol. 2015 Jan 15;194(2):553-9. doi: 10.4049/jimmunol.1402058. Epub 2014 Dec 5.

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

Author information

1
Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany; Institute of Immunology, Charité Berlin, 12200 Berlin, Germany;
2
Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany;
3
Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany; Organ-Specific Immune Regulation, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; and.
4
Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany; Institute of Biology, Humboldt University Berlin, 10115 Berlin, Germany.
5
Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany; Institute of Immunology, Charité Berlin, 12200 Berlin, Germany; thomas.schueler@med.ovgu.de.

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-γR signaling in CD8(+) T cells promotes TM formation in response to weak, but not strong, TCR agonists. The IFN-γ-sensitive accumulation of TMs correlates with reduced mammalian target of rapamycin activation and the accumulation of long-lived CD62L(hi)Bcl-2(hi)Eomes(hi) TMPs. Reconstitution of mammalian target of rapamycin or IFN-γR signaling is sufficient to block this process. Hence, our data suggest that IFN-γR 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.

PMID:
25480562
DOI:
10.4049/jimmunol.1402058
[Indexed for MEDLINE]
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