| First Author | Di Santo JP | Year | 1999 |
| Journal | J Exp Med | Volume | 189 |
| Issue | 3 | Pages | 563-74 |
| PubMed ID | 9927518 | Mgi Jnum | J:52569 |
| Mgi Id | MGI:1329769 | Doi | 10.1084/jem.189.3.563 |
| Citation | Di Santo JP, et al. (1999) The common cytokine receptor gamma chain and the pre-T cell receptor provide independent but critically overlapping signals in early alpha/beta T cell development. J Exp Med 189(3):563-74 |
| abstractText | 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- 7Ralpha coupled to the common cytokine receptor gamma chain, gammac) play a dominant role in early thymopoiesis. However, alpha/beta T cell development in IL-7-, IL-7Ralpha-, and gammac-deficient mice is only partially compromised, suggesting that additional pathways can rescue alpha/beta T lineage cells in these mice. We have investigated the potential interdependence of gammac- and pre-TCR-dependent pathways during intrathymic alpha/beta T cell differentiation. We demonstrate that gammac-dependent cytokines do not appear to be required for normal pre-TCR function, and that the rate-limiting step in alpha/beta T cell development in gammac- mice does not involve TCR-beta chain rearrangements, but rather results from poor maintenance of early thymocytes. Moreover, mice double mutant for both gammac and pre-Talpha 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 gammac- independent signal which allows alpha/beta T cell development in gammac- mice. Thus, a series of overlapping signals derived from cytokine and T cell receptors guide the process of alpha/beta thymocyte development. |
