Unstimulated human CD4 lymphocytes express a cytoplasmic immature form of the common cytokine receptor gamma-chain

As a component of various cytokine receptors, common cytokine receptor gamm a -chain (gamma (c)) is essential in the development of the immune system a nd plays an important role in different stages of inflammatory and immune r esponses. Here we establish that resting CD4 T cells and the Jurkat CD4 T c ell line do not express the mature form of gamma (c) (64 kDa) recognized by mAb Tugh4. However, these cells constitutively transcribe the correspondin g gamma (c) gene. This apparent paradox was solved by the demonstration tha t polyclonal anti-gamma (c) Abs detected endoglycosidase-H-sensitive immatu re forms of gamma (c) (54-58 kDa) expressed by quiescent CD4 T lymphocytes and Jurkat cells. Immature gamma (c) is characterized as an intracellular c omponent localized in the endoplasmic reticulum. Pulse-chase analysis shows that the immature gamma (c) is rapidly degraded after synthesis. After act ivation of CD4 T lymphocytes, and as seen in the CD4 T cell line Kit 225, t he endoglycosidase-H-resistant mature form of gamma (c), is detectable at t he cell surface and in the endosomal compartment. For the first time, our r esults demonstrate that a cytokine receptor chain may be constitutively pro duced as an immature form. Furthermore, this supports the notion that expre ssion of the functional form of gamma (c), may require intracellular intera ctions with lineage- or subset-specific molecular partners.