Differential requirement of the cytoplasmic subregions of gamma c chain inT cell development and function

The common cytokine receptor gamma chain (gamma c), a shared component of t he receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, is critical for the dev elopment and function of lymphocytes. The cytoplasmic domain of gamma c con sists of 85 aa, in which the carboxyl-terminal 48 aa are essential for its interaction with and activation of the Janus kinase, Jak3. Evidence has bee n provided that Jak3-independent signals might be transmitted via the resid ual membrane-proximal region; however, its role in vivo remains totally unk nown. In the present study, we expressed mutant forms of gamma c, which lac k either most of the cytoplasmic domain or only the membrane-distal Jak3-bi nding region, on a gamma c null background. We demonstrate that, unlike gam ma c or Jak3 null mice, expression of the latter, but not the former mutant , restores T lymphopoiesis in vivo, accompanied by strong expression of Bcl -2. On the other hand, the in vitro functions of the restored T cells still remained impaired. These results not only reveal the hitherto unknown role of the gamma c membrane-proximal region, but also suggest the differential requirement of the cytoplasmic subregions of gamma c in T cell development and function.