MONOCLONAL-ANTIBODIES TO THE COMMON GAMMA-CHAIN AS CYTOKINE RECEPTOR ANTAGONISTS IN-VIVO - EFFECT ON INTRATHYMIC AND INTESTINAL INTRAEPITHELIAL T-LYMPHOCYTE DEVELOPMENT

Mice lacking a functional gamma c subunit of cytokine receptors exhibi t profound defects in the development of multiple lymphoid Lineages. T o investigate the role of gamma c-dependent cytokines in T cell develo pment, the phenotype of developing T cells was compared in interleukin (IL)-7R alpha-deficient mice and anti-gamma c mAb-treated chimeric mi ce reconstituted,vith adult bone marrow cells or subsets of pro-T cell s. These studies indicate that gamma c contributes to T cell developme nt 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 thym ic T cell development. By contrast, substantial intestinal intraepithe lial lymphocytes (IEL) development was observed in the intestinal intr aepithelium in both types of mice, Analysis of IL-7Ra-deficient mice i ndicates that the IL-7/IL-7R system is critical only for the developme nt of TCR gamma delta(+) IEL, However, the inhibitory activity of the anti-gamma c mAb in the chimeric mouse model suggests that additional gamma c-utilizing cytokines regulate the development of the remaining subsets of IEL.