The Role of the Common Gamma Chain of the IL-2, IL-4, IL-7 and IL-15 Receptors in Development of Lymphocytes. Constitutive Expression of Bcl-2 does not Rescue the Developmental Defects in Gamma Common-Deficient Mice

Abstract

It is firmly established that cytokines are involved in development of hematopoietic cells. Until recently it was not known whether cytokines are involved in development of lymphoid cells. Initially, interleukin (IL)-2 and IL-4 were considered to be candidates essential for lymphoid development. However, this turned out not to be the case since mice deficient for IL-2 [1], IL-4 [2] or both [3] had no obvious defects with regard to development of T and B cells. Nonetheless, it became clear that cytokines do play an essential role in T cell development when the molecular defect underlying the X chromosome linked severe combined immunodeficiency (X-SCID) was determined [4]. These patients have no T or NK cells but B cells are present in normal numbers. It turned out that these patients have mutations in the gamma chain of the IL-2 receptor complex [4]. As it was already known that IL-2 is not essential for T cell development, it was suspected that this component of the IL-2R was also part of receptors for other cytokines. This suspicion was confirmed soon thereafter when it was found that the IL-2Rγ chain is also a component of the receptors of IL-4, IL-7, IL-9 and IL-15 [5–7]. Therefore, the IL-2Rγ chain is now commonly referred to as the gamma common (γc) chain. Studies with IL-7 [8] and IL-7Rα chain deficient mice [9] havve made clear that IL-7 is the critical γc ligand involved in T cell development. Like the γc deficient mice [10], these mice have a thymus that is only 10% in size of the wild type thymus.