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J Leukoc Biol. 1998 Jun;63(6):643-9.

Monoclonal antibodies to the common gamma-chain as cytokine receptor antagonists in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte development.

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  • 1Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101, USA. tmalek@mednet.med.miami.edu

Abstract

Mice lacking a functional gamma c subunit of cytokine receptors exhibit profound defects in the development of multiple lymphoid lineages. To investigate the role of gamma c-dependent cytokines in T cell development, the phenotype of developing T cells was compared in interleukin (IL)-7Ralpha-deficient mice and anti-gamma c mAb-treated chimeric mice reconstituted with adult bone marrow cells or subsets of pro-T cells. These studies indicate that gamma c contributes to T cell development at multiple stages of pro-T cell maturation and that IL-7/IL-7R is the primary cytokine for thymic-dependent T cell development. However, our data also implicate other gamma c-dependent cytokines during thymic T cell development. By contrast, substantial intestinal intraepithelial lymphocytes (IEL) development was observed in the intestinal intraepithelium in both types of mice. Analysis of IL-7Ralpha-deficient mice indicates that the IL-7/IL-7R system is critical only for the development of TCR gammadelta+ IEL. However, the inhibitory activity of the anti-deltac mAb in the chimeric mouse model suggests that additional gamma cutilizing cytokines regulate the development of the remaining subsets of IEL.

PMID:
9620654
[PubMed - indexed for MEDLINE]
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