Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice

Loss of interleukin (IL)-7 or the IL-7 receptor alpha (IL-7Rα, CD127) results in severe immunodeficiencies in mice and humans. To more precisely identify signals governing IL-7 function in vivo, we have disrupted the IL-7Rα Y449XXM motif in mice by knock-in mutagenesis (IL-7Rα(449F)). Thymic precurs...

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Autores principales: Osborne, Lisa C., Dhanji, Salim, Snow, Jonathan W., Priatel, John J., Ma, Melissa C., Miners, M. Jill, Teh, Hung-Sia, Goldsmith, Mark A., Abraham, Ninan
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137912/
https://www.ncbi.nlm.nih.gov/pubmed/17325202
http://dx.doi.org/10.1084/jem.20061871
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author Osborne, Lisa C.
Dhanji, Salim
Snow, Jonathan W.
Priatel, John J.
Ma, Melissa C.
Miners, M. Jill
Teh, Hung-Sia
Goldsmith, Mark A.
Abraham, Ninan
author_facet Osborne, Lisa C.
Dhanji, Salim
Snow, Jonathan W.
Priatel, John J.
Ma, Melissa C.
Miners, M. Jill
Teh, Hung-Sia
Goldsmith, Mark A.
Abraham, Ninan
author_sort Osborne, Lisa C.
collection PubMed
description Loss of interleukin (IL)-7 or the IL-7 receptor alpha (IL-7Rα, CD127) results in severe immunodeficiencies in mice and humans. To more precisely identify signals governing IL-7 function in vivo, we have disrupted the IL-7Rα Y449XXM motif in mice by knock-in mutagenesis (IL-7Rα(449F)). Thymic precursors were reduced in number in IL-7Rα(449F) mice, but in marked contrast to IL-7Rα(−/−) knockout mice, thymocytes and peripheral T cells developed normally. Strikingly, Listeria infection revealed that CD4 and CD8 T cells had different requirements for IL-7Rα signals. CD4 T cells failed to mount a primary response, but despite normal CD8 primary responses, maintenance of CD8 memory was impaired in IL-7Rα(449F) mice. Furthermore, we show that Bcl-2 is IL-7Rα Y449 independent and insufficient for IL-7–mediated maintenance of CD8 memory.
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spelling pubmed-21379122007-12-13 Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice Osborne, Lisa C. Dhanji, Salim Snow, Jonathan W. Priatel, John J. Ma, Melissa C. Miners, M. Jill Teh, Hung-Sia Goldsmith, Mark A. Abraham, Ninan J Exp Med Articles Loss of interleukin (IL)-7 or the IL-7 receptor alpha (IL-7Rα, CD127) results in severe immunodeficiencies in mice and humans. To more precisely identify signals governing IL-7 function in vivo, we have disrupted the IL-7Rα Y449XXM motif in mice by knock-in mutagenesis (IL-7Rα(449F)). Thymic precursors were reduced in number in IL-7Rα(449F) mice, but in marked contrast to IL-7Rα(−/−) knockout mice, thymocytes and peripheral T cells developed normally. Strikingly, Listeria infection revealed that CD4 and CD8 T cells had different requirements for IL-7Rα signals. CD4 T cells failed to mount a primary response, but despite normal CD8 primary responses, maintenance of CD8 memory was impaired in IL-7Rα(449F) mice. Furthermore, we show that Bcl-2 is IL-7Rα Y449 independent and insufficient for IL-7–mediated maintenance of CD8 memory. The Rockefeller University Press 2007-03-19 /pmc/articles/PMC2137912/ /pubmed/17325202 http://dx.doi.org/10.1084/jem.20061871 Text en Copyright © 2007, The Rockefeller University Press 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 Articles
Osborne, Lisa C.
Dhanji, Salim
Snow, Jonathan W.
Priatel, John J.
Ma, Melissa C.
Miners, M. Jill
Teh, Hung-Sia
Goldsmith, Mark A.
Abraham, Ninan
Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice
title Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice
title_full Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice
title_fullStr Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice
title_full_unstemmed Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice
title_short Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice
title_sort impaired cd8 t cell memory and cd4 t cell primary responses in il-7rα mutant mice
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137912/
https://www.ncbi.nlm.nih.gov/pubmed/17325202
http://dx.doi.org/10.1084/jem.20061871
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