J. Exp. Med., Volume 189, Number 3, February 1, 1999 563-574

The Common Cytokine Receptor  Chain and the Pre-T Cell Receptor Provide Independent but Critically Overlapping Signals in Early / T Cell Development

By James P. Di Santo,^* Iannis Aifantis,^§ Eleftheria Rosmaraki,^* Corinne Garcia,^§ Jacqueline Feinberg,^§ Hans Jörg Fehling, Alain Fischer,^* Harald von Boehmer,^§ and Benedita Rocha

From the ^* Institut National de la Santé et de la Recherche Médicale (INSERM) U429, Hôpital Necker-Enfants Malades, F-75743 Paris, France;  INSERM U345 and ^§ U373, CHU Necker, F-75730 Paris, France; and the  Basel Institute for Immunology, CH-4005 Basel, Switzerland

Intracellular signals emanating from cytokine and antigen receptors are integrated during the process of intrathymic development. Still, the relative contributions of cytokine receptor signaling to pre-T cell receptor (TCR) and TCR-mediated differentiation remain undefined. Interleukin (IL)-7 interactions with its cognate receptor complex (IL-7R coupled to the common cytokine receptor  chain, _c) play a dominant role in early thymopoiesis. However, / T cell development in IL-7-, IL-7R-, and _c-deficient mice is only partially compromised, suggesting that additional pathways can rescue / T lineage cells in these mice. We have investigated the potential interdependence of _c- and pre-TCR-dependent pathways during intrathymic / T cell differentiation. We demonstrate that _c-dependent cytokines do not appear to be required for normal pre-TCR function, and that the rate-limiting step in / T cell development in _c mice does not involve TCR- chain rearrangements, but rather results from poor maintenance of early thymocytes. Moreover, mice double mutant for both _c and pre-T show vastly reduced thymic cellularity and a complete arrest of thymocyte differentiation at the CD44⁺CD25⁺ cell stage. These observations demonstrate that the pre-TCR provides the _c-independent signal which allows / T cell development in _c mice. Thus, a series of overlapping signals derived from cytokine and T cell receptors guide the process of / thymocyte development.

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