IL-2Rβ/IL-7Rα doubly deficient mice recapitulate the thymic and intraepithelial lymphocyte (IEL) developmental defects of γc(-/-) mice: Roles for both IL-2 and IL-15 in CD8αα IEL development

Brian O. Porter, Thomas Malek

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Abstract

IL-7Rα-chain-deficient (IL-7Rα(-/-)) and common γ chain-deficient (γc(-/-)) mice both exhibit abnormal thymic and intestinal intraepithelial lymphocyte (IEL) development, but the developmental inhibition is not equivalent. In this report, we assessed whether the defects in T cell development associated with γc(-/-) mice were due to currently defined γc- dependent cytokines by cross-breeding IL-7Rα(-/-) mice to mice lacking either IL-2, IL-4, or IL-2Rβ. IL-2/IL-7Rα and IL-4/IL-7Rα double knockout (DKO) mice demonstrated equivalent thymic development to IL-7Rα(-/-) mice, whereas IL-2Rβ/IL-7Rα DKO mice, which lack IL-2, IL-7, and IL-15 signaling, displayed thymic T cell defects identical to γc(-/-) mice. Collectively, these data indicate that of the γc-dependent cytokines, only IL-7 and IL-15 contribute to the progression and production of thymic T cells. In the IEL, IL7Rα(-/-) mice selectively lack CD8αα TCRγδ cells, whereas IL-2Rβ(-/-) mice show a significant reduction in all CD8αα cells. IL-2(-/-) and IL- 2/IL-7Rα DKO mice demonstrated a reduction in CD8αα IELs to nearly the same extent as IL-2Rβ(-/-) mice, indicating that IL-2 functions in CD8αα IEL development. Moreover, IL-2Rβ/IL-7Rα DKO mice lacked nearly all TCR- bearing IEL, again recapitulating the phenotype of γc(-/-) mice. Thus, these data point to the importance of IL-2, IL-7, and IL-15 as the γc-dependent cytokines essential for IEL development.

Original languageEnglish
Pages (from-to)5906-5912
Number of pages7
JournalJournal of Immunology
Volume163
Issue number11
StatePublished - Dec 1 1999

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Interleukin-15
Interleukin-2
Lymphocytes
Knockout Mice
Interleukin-7
Cytokines
T-Lymphocytes
Interleukin-4
Breeding
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

@article{c28300c21e6242a7b27d24403b42e04c,
title = "IL-2Rβ/IL-7Rα doubly deficient mice recapitulate the thymic and intraepithelial lymphocyte (IEL) developmental defects of γc(-/-) mice: Roles for both IL-2 and IL-15 in CD8αα IEL development",
abstract = "IL-7Rα-chain-deficient (IL-7Rα(-/-)) and common γ chain-deficient (γc(-/-)) mice both exhibit abnormal thymic and intestinal intraepithelial lymphocyte (IEL) development, but the developmental inhibition is not equivalent. In this report, we assessed whether the defects in T cell development associated with γc(-/-) mice were due to currently defined γc- dependent cytokines by cross-breeding IL-7Rα(-/-) mice to mice lacking either IL-2, IL-4, or IL-2Rβ. IL-2/IL-7Rα and IL-4/IL-7Rα double knockout (DKO) mice demonstrated equivalent thymic development to IL-7Rα(-/-) mice, whereas IL-2Rβ/IL-7Rα DKO mice, which lack IL-2, IL-7, and IL-15 signaling, displayed thymic T cell defects identical to γc(-/-) mice. Collectively, these data indicate that of the γc-dependent cytokines, only IL-7 and IL-15 contribute to the progression and production of thymic T cells. In the IEL, IL7Rα(-/-) mice selectively lack CD8αα TCRγδ cells, whereas IL-2Rβ(-/-) mice show a significant reduction in all CD8αα cells. IL-2(-/-) and IL- 2/IL-7Rα DKO mice demonstrated a reduction in CD8αα IELs to nearly the same extent as IL-2Rβ(-/-) mice, indicating that IL-2 functions in CD8αα IEL development. Moreover, IL-2Rβ/IL-7Rα DKO mice lacked nearly all TCR- bearing IEL, again recapitulating the phenotype of γc(-/-) mice. Thus, these data point to the importance of IL-2, IL-7, and IL-15 as the γc-dependent cytokines essential for IEL development.",
author = "Porter, {Brian O.} and Thomas Malek",
year = "1999",
month = "12",
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journal = "Journal of Immunology",
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TY - JOUR

T1 - IL-2Rβ/IL-7Rα doubly deficient mice recapitulate the thymic and intraepithelial lymphocyte (IEL) developmental defects of γc(-/-) mice

T2 - Roles for both IL-2 and IL-15 in CD8αα IEL development

AU - Porter, Brian O.

AU - Malek, Thomas

PY - 1999/12/1

Y1 - 1999/12/1

N2 - IL-7Rα-chain-deficient (IL-7Rα(-/-)) and common γ chain-deficient (γc(-/-)) mice both exhibit abnormal thymic and intestinal intraepithelial lymphocyte (IEL) development, but the developmental inhibition is not equivalent. In this report, we assessed whether the defects in T cell development associated with γc(-/-) mice were due to currently defined γc- dependent cytokines by cross-breeding IL-7Rα(-/-) mice to mice lacking either IL-2, IL-4, or IL-2Rβ. IL-2/IL-7Rα and IL-4/IL-7Rα double knockout (DKO) mice demonstrated equivalent thymic development to IL-7Rα(-/-) mice, whereas IL-2Rβ/IL-7Rα DKO mice, which lack IL-2, IL-7, and IL-15 signaling, displayed thymic T cell defects identical to γc(-/-) mice. Collectively, these data indicate that of the γc-dependent cytokines, only IL-7 and IL-15 contribute to the progression and production of thymic T cells. In the IEL, IL7Rα(-/-) mice selectively lack CD8αα TCRγδ cells, whereas IL-2Rβ(-/-) mice show a significant reduction in all CD8αα cells. IL-2(-/-) and IL- 2/IL-7Rα DKO mice demonstrated a reduction in CD8αα IELs to nearly the same extent as IL-2Rβ(-/-) mice, indicating that IL-2 functions in CD8αα IEL development. Moreover, IL-2Rβ/IL-7Rα DKO mice lacked nearly all TCR- bearing IEL, again recapitulating the phenotype of γc(-/-) mice. Thus, these data point to the importance of IL-2, IL-7, and IL-15 as the γc-dependent cytokines essential for IEL development.

AB - IL-7Rα-chain-deficient (IL-7Rα(-/-)) and common γ chain-deficient (γc(-/-)) mice both exhibit abnormal thymic and intestinal intraepithelial lymphocyte (IEL) development, but the developmental inhibition is not equivalent. In this report, we assessed whether the defects in T cell development associated with γc(-/-) mice were due to currently defined γc- dependent cytokines by cross-breeding IL-7Rα(-/-) mice to mice lacking either IL-2, IL-4, or IL-2Rβ. IL-2/IL-7Rα and IL-4/IL-7Rα double knockout (DKO) mice demonstrated equivalent thymic development to IL-7Rα(-/-) mice, whereas IL-2Rβ/IL-7Rα DKO mice, which lack IL-2, IL-7, and IL-15 signaling, displayed thymic T cell defects identical to γc(-/-) mice. Collectively, these data indicate that of the γc-dependent cytokines, only IL-7 and IL-15 contribute to the progression and production of thymic T cells. In the IEL, IL7Rα(-/-) mice selectively lack CD8αα TCRγδ cells, whereas IL-2Rβ(-/-) mice show a significant reduction in all CD8αα cells. IL-2(-/-) and IL- 2/IL-7Rα DKO mice demonstrated a reduction in CD8αα IELs to nearly the same extent as IL-2Rβ(-/-) mice, indicating that IL-2 functions in CD8αα IEL development. Moreover, IL-2Rβ/IL-7Rα DKO mice lacked nearly all TCR- bearing IEL, again recapitulating the phenotype of γc(-/-) mice. Thus, these data point to the importance of IL-2, IL-7, and IL-15 as the γc-dependent cytokines essential for IEL development.

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