Abnormal development of intestinal intraepithelial lymphocytes and peripheral natural killer cells in mice lacking the IL-2 receptor beta chain.

Abstract

The interleukin-2 receptor beta chain (IL-2R beta) is expressed on a variety of hematopoietic cell types, including natural killer (NK) cells and nonconventional T lymphocyte subsets such as intestinal intraepithelial lymphocytes (IEL). However, the importance of IL-2R beta-mediated signaling in the growth and development of these cells has yet to be clearly established. We have investigated IEL and NK cells in mice deficient for IL-2R beta and describe here striking defects in the development of these cells. IL-2R beta-/- mice exhibited an abnormal IEL cell population, characterized by a dramatic reduction in T cell receptor alpha beta CD8 alpha alpha and T cell receptor gamma delta lymphocytes. This selective decrease indicates that IEL can be classified into those whose development and/or differentiation is dependent on IL-2R beta function and those for which IL-2R beta-mediated signaling is not essential. NK cell development was also found to be disrupted in IL-2R beta-deficient mice, characterized by a reduction in NK1.1+CD3- cells in the peripheral circulation and an absence of NK cytotoxic activity in vitro. The dependence of NK cells and certain subclasses of IEL cells on IL-2R beta expression points to an essential role for signaling through this receptor, presumably by IL-2 and/or IL-15, in the development of lymphocyte-subsets of extrathymic origin.