| First Author | Swat W | Year | 2006 |
| Journal | Blood | Volume | 107 |
| Issue | 6 | Pages | 2415-22 |
| PubMed ID | 16304053 | Mgi Jnum | J:125791 |
| Mgi Id | MGI:3759930 | Doi | 10.1182/blood-2005-08-3300 |
| Citation | Swat W, et al. (2006) Essential role of PI3Kdelta and PI3Kgamma in thymocyte survival. Blood 107(6):2415-22 |
| abstractText | Class 1 phosphoinositide 3-kinases (PI3Ks), consisting of PI3Kalpha, beta, gamma, and delta, are a family of intracellular signaling molecules that play important roles in cell-mediated immune responses. In thymocytes, however, their role is less clear, although PI3Kgamma is postulated to partially contribute to pre-TCR-dependent differentiation. We now report that PI3Kdelta, in conjunction with PI3Kgamma, is required for thymocyte survival and ultimately for T-cell production. Surprisingly, genetic deletion of the p110delta and p110gamma catalytic subunits resulted in a dramatic reduction in thymus size, cellularity, and lack of corticomedullary differentiation. Total thymocyte counts in these animals were 27-fold lower than in wild-type (WT) controls because of a diminished number of CD4+ CD8+ double-positive (DP) cells and were associated with T-cell depletion in blood and in secondary lymphoid organs. Moreover, this alteration in the DP population was intrinsic to thymocytes, because the reconstitution of p110gammadelta-/- animals with WT fetal liver cells restored the proportions of all thymocyte populations to those in WT controls. The observed defects were related to massive apoptosis in the DP population; TCRB expression, pre-TCR selection, and generation of DP cells appeared relatively unperturbed. Thus, class 1 PI3Ks work in concert to protect developing thymocytes from apoptosis. |
