T-LYMPHOCYTE DIFFERENTIATION AND PROLIFERATION IN THE ABSENCE OF THE CYTOPLASMIC TAIL OF THE COMMON CYTOKINE RECEPTOR GAMMA(C) CHAIN IN A SEVERE COMBINED IMMUNE-DEFICIENCY X1 PATIENT

Mutation of the gamma(c) chain common to interleukin-2 (IL-2), IL-4, I L-7, IL-9, and IL-15 receptors has been shown to be responsible for th e X chromosome-linked severe combined immune deficiency (SCIDX1). Huma n SCIDX1 patients are characterized by an absence of T and natural kil ler cell differentiation. We report the case of a SCIDX1 patient who f irst had few detectable peripheral T cells, then developed, after hapl oidentical T-depleted bone marrow transplantation (BMT), up to 2,000/m u L autologous T cells. These T cells have persisted over 8 years afte r BMT and were able to proliferate in the presence of mitogens and of some antigens, although to a lesser extent than control T cells. A sto p mutation was identified which predicts that the major part of the cy toplasmic tail of gamma(c) is truncated. This mutation does not affect high-affinity IL-2 binding, but it partly decreases IL-2 endocytosis and prevents the downmodulation of the IL-2-receptor beta chain and th e tyrosine phosphorylation of Jak 3 protein in response to IL-2. This report raises questions concerning the role of the gamma(c) chain in I L-2 receptor endocytosis and in T-cell development and differentiation . (C) 1996 by The American Society of Hematology.