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J. Exp. Med.,
Volume 189, Number 3, February 1, 1999 563-574
Chain and the Pre-T
Cell Receptor Provide Independent but Critically
Overlapping Signals in Early
/
T Cell Development
By


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