| First Author | Wiede F | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 3073 | PubMed ID | 24445916 |
| Mgi Jnum | J:206438 | Mgi Id | MGI:5550290 |
| Doi | 10.1038/ncomms4073 | Citation | Wiede F, et al. (2014) PTPN2 attenuates T-cell lymphopenia-induced proliferation. Nat Commun 5:3073 |
| abstractText | 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. |
