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

Published

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Malek, TR; Levy, RB; Adkins, B; He, YW

Published Date

  • June 1998

Published In

Volume / Issue

  • 63 / 6

Start / End Page

  • 643 - 649

PubMed ID

  • 9620654

Pubmed Central ID

  • 9620654

International Standard Serial Number (ISSN)

  • 0741-5400

Digital Object Identifier (DOI)

  • 10.1002/jlb.63.6.643

Language

  • eng

Conference Location

  • United States