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Crucial Role of Jak3 in Negative Selection of Self-reactive T Cells

Jak3 mediates growth signals through cytokine receptors such as interleukin-2 (IL-2), IL-4, and IL-7, and its deficiency results in autosomal recessive SCID in mice and humans. In spite of the severely reduced number of lymphocytes in Jak3-deficient mice, the differentiation profile of thymocytes wa...

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Autores principales: Saijo, Kaoru, Park, Seung Yong, Ishida, Yasuo, Arase, Hisashi, Saito, Takashi
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196119/
https://www.ncbi.nlm.nih.gov/pubmed/9016883
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author Saijo, Kaoru
Park, Seung Yong
Ishida, Yasuo
Arase, Hisashi
Saito, Takashi
author_facet Saijo, Kaoru
Park, Seung Yong
Ishida, Yasuo
Arase, Hisashi
Saito, Takashi
author_sort Saijo, Kaoru
collection PubMed
description Jak3 mediates growth signals through cytokine receptors such as interleukin-2 (IL-2), IL-4, and IL-7, and its deficiency results in autosomal recessive SCID in mice and humans. In spite of the severely reduced number of lymphocytes in Jak3-deficient mice, the differentiation profile of thymocytes was normal and mature T cells accumulated in the periphery with age. However, we found that self-reactive T cells were not deleted in the thymus and the peripheral tissues in Jak3-deficient mice. All peripheral T cells were in the activation state and thus were unable to be activated further, as demonstrated by the failure of eliciting Ca(2+) response upon T cell receptor (TCR) stimulation. From the analysis of TCR-transgenic Jak3-deficient mice, only self-reactive T cells appeared to be in the activated state and anergic. These findings demonstrate a crucial function of Jak3 in the negative selection of autoreactive T cells and the maintenance of functional peripheral T cells.
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spelling pubmed-21961192008-04-16 Crucial Role of Jak3 in Negative Selection of Self-reactive T Cells Saijo, Kaoru Park, Seung Yong Ishida, Yasuo Arase, Hisashi Saito, Takashi J Exp Med Brief Definitive Report Jak3 mediates growth signals through cytokine receptors such as interleukin-2 (IL-2), IL-4, and IL-7, and its deficiency results in autosomal recessive SCID in mice and humans. In spite of the severely reduced number of lymphocytes in Jak3-deficient mice, the differentiation profile of thymocytes was normal and mature T cells accumulated in the periphery with age. However, we found that self-reactive T cells were not deleted in the thymus and the peripheral tissues in Jak3-deficient mice. All peripheral T cells were in the activation state and thus were unable to be activated further, as demonstrated by the failure of eliciting Ca(2+) response upon T cell receptor (TCR) stimulation. From the analysis of TCR-transgenic Jak3-deficient mice, only self-reactive T cells appeared to be in the activated state and anergic. These findings demonstrate a crucial function of Jak3 in the negative selection of autoreactive T cells and the maintenance of functional peripheral T cells. The Rockefeller University Press 1997-01-20 /pmc/articles/PMC2196119/ /pubmed/9016883 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Saijo, Kaoru
Park, Seung Yong
Ishida, Yasuo
Arase, Hisashi
Saito, Takashi
Crucial Role of Jak3 in Negative Selection of Self-reactive T Cells
title Crucial Role of Jak3 in Negative Selection of Self-reactive T Cells
title_full Crucial Role of Jak3 in Negative Selection of Self-reactive T Cells
title_fullStr Crucial Role of Jak3 in Negative Selection of Self-reactive T Cells
title_full_unstemmed Crucial Role of Jak3 in Negative Selection of Self-reactive T Cells
title_short Crucial Role of Jak3 in Negative Selection of Self-reactive T Cells
title_sort crucial role of jak3 in negative selection of self-reactive t cells
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196119/
https://www.ncbi.nlm.nih.gov/pubmed/9016883
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