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

Thomas R. Malek, Robert B. Levy, Becky Adkins, You Wen He

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Mice lacking a functional γc subunit of cytokine receptors exhibit profound defects in the development of multiple lymphoid lineages. To investigate the role of γc-dependent cytokines in T cell development, the phenotype of developing T cells was compared in interleukin (IL)-7Rα- deficient mice and anti-γc mAb-treated chimeric mice reconstituted with adult bone marrow cells or subsets of pro-T cells. These studies indicate that γc 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 γc-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-7Rα- deficient mice indicates that the IL-7/IL-7R system is critical only for the development of TCR γδ+ IEL. However, the inhibitory activity of the anti- γc mAb in the chimeric mouse model suggests that additional γc-utilizing cytokines regulate the development of the remaining subsets of IEL.

Original languageEnglish (US)
Pages (from-to)643-649
Number of pages7
JournalJournal of Leukocyte Biology
Volume63
Issue number6
DOIs
StatePublished - Jun 1998

Keywords

  • IL-7
  • IL-7R
  • pro-T cells
  • X-linked SCID

ASJC Scopus subject areas

  • Cell Biology

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