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

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dc.creator Andreu-Sánchez, Jose L.
dc.creator Moreno de Alborán, Ignacio
dc.creator Marcos, Miguel A. R.
dc.creator Sánchez-Movilla, Arsenio
dc.creator Martínez-Alonso, Carlos
dc.creator Kroemer, Guido
dc.date 2008-04-23T11:07:40Z
dc.date 2008-04-23T11:07:40Z
dc.date 1991-06
dc.date.accessioned 2017-01-31T01:03:12Z
dc.date.available 2017-01-31T01:03:12Z
dc.identifier The Journal of Experimental Medicine, Volume 173, June 1991, pp. 1323-1329
dc.identifier 0022-1007
dc.identifier http://hdl.handle.net/10261/3694
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3694
dc.description El copyright pertenece a The Rockefeller University Press
dc.description Under 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.
dc.description Peer reviewed
dc.format 977218 bytes
dc.format application/pdf
dc.language eng
dc.publisher Rockefeller University Press
dc.rights openAccess
dc.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
dc.type Artículo


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