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





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,
/β T cell development in IL-7–, IL-7R
–, and
c-deficient mice is only partially compromised, suggesting that additional pathways can rescue
/β T lineage cells in these mice. We have investigated the potential interdependence of
c- and pre-TCR–dependent pathways during intrathymic
/β 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
/β T cell development in
c– mice does not involve TCR-β 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
/β T cell development in
c– mice. Thus, a series of overlapping signals derived from cytokine and T cell receptors guide the process of
/β thymocyte development.
Key Words: thymus interleukin lymphocyte development knockout
1 Abbreviations used in this paper: BrdU, bromo-deoxyuridine; DN, double negative; DP, double positive;
c, common cytokine receptor
chain; RAG, recombination activating gene; SP, single positive; TN, triple negative; Tg, transgene; TRI, Tricolor.
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