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Title

Interleukin 2 abrogates the nonresponsive state of T cells expressing a forbidden T cell receptor repertoire and induces autoimmune disease in neonatally thymectomized mice

AuthorsAndreu-Sánchez, Jose L.; Moreno de Alborán, Ignacio; Marcos, Miguel A. R.; Sánchez-Movilla, Arsenio; Martínez-Alonso, Carlos; Kroemer, Guido
Issue DateJun-1991
PublisherRockefeller University Press
CitationThe Journal of Experimental Medicine, Volume 173, June 1991, pp. 1323-1329
AbstractUnder physiological conditions, the vast majority of T cells differentiate in the thymus, an organ that provides an optimal microenvironment for T cell maturation and shapes the T cell repertoire via positive and negative selection processes. In the present report, we demonstrate that neonatal thymectomy of CBA/H mice results in a diminution of T cells in peripheral lymphoid organs (spleen, lymph nodes), but is followed by a marked transient (12 wk) increase in Thy-1+ CD3+ cells in the peritoneal cavity. These cells exhibit predominantly a double-negative (CD4 - CD8 - ) phenotype among which products of the T cell receptor (TCR) VO11 gene family (i.e., an I-Ereactive TCR normally deleted in I-E-bearing CBA/H mice) are selectively overexpressed . This observation suggests that, under athymic conditions, T cell differentiation and/or accumulation may occur in the peritoneal cavity. Intraperitoneal inoculation of an interleukin 2 (IL2) vaccinia virus construct that releases high titers of human IIr2 in vivo induces conversion of these doublenegative T cells to either CD4+CD8 - or CD4-CD8+ single positives, and allows in vitro stimulation of TCR V,311-bearing cells with a clonotypic antiVO antibody. Since IL-2 induces autoimmune manifestations (DNA autoantibodies, rheumatoid factors, and interstitial nephritis) in thymectomized CBA/H mice, but not in sham-treated littermates, this lymphokine is likely to enhance the autoaggressive function of T cells that bear forbidden, potentially autoreactive TCR gene products and that are normally deleted in the thymus.
DescriptionEl copyright pertenece a The Rockefeller University Press
URIhttp://hdl.handle.net/10261/3694
ISSN0022-1007
Appears in Collections:(CNB) Artículos
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