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Nat Commun. 2014;5:3073. doi: 10.1038/ncomms4073.

PTPN2 attenuates T-cell lymphopenia-induced proliferation.

Author information

1
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
2
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.

Abstract

When the peripheral T-cell pool is depleted, T cells undergo homoeostatic expansion. This expansion is reliant on the recognition of self-antigens and/or cytokines, in particular interleukin-7. The T cell-intrinsic mechanisms that prevent excessive homoeostatic T-cell responses and consequent overt autoreactivity remain poorly defined. Here we show that protein tyrosine phosphatase N2 (PTPN2) is elevated in naive T cells leaving the thymus to restrict homoeostatic T-cell proliferation and prevent excess responses to self-antigens in the periphery. PTPN2-deficient CD8(+) T cells undergo rapid lymphopenia-induced proliferation (LIP) when transferred into lymphopenic hosts and acquire the characteristics of antigen-experienced effector T cells. The enhanced LIP is attributed to elevated T-cell receptor-dependent, but not interleukin-7-dependent responses, results in a skewed T-cell receptor repertoire and the development of autoimmunity. Our results identify a major mechanism by which homoeostatic T-cell responses are tuned to prevent the development of autoimmune and inflammatory disorders.

PMID:
24445916
DOI:
10.1038/ncomms4073
[Indexed for MEDLINE]

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