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

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. J. Leukoc. Biol. 63: 643–649; 1998.