| First Author | Hua DR | Year | 2003 |
| Journal | Eur J Immunol | Volume | 33 |
| Issue | 7 | Pages | 1899-906 |
| PubMed ID | 12811850 | Mgi Jnum | J:84395 |
| Mgi Id | MGI:2667544 | Doi | 10.1002/eji.200323720 |
| Citation | Hua DR, et al. (2003) T cell-specific gene targeting reveals that alpha4 is required for early T cell development. Eur J Immunol 33(7):1899-906 |
| abstractText | Alpha4-mediated signaling is involved in a variety of functions in mammalian cells. To determine whether this is true for immunocompetent cells, we generated mutant (Lck-alpha4-) mice in which the alpha4 gene was deleted in a T cell-specific manner using the Cre/loxP system. These mice showed impaired early T cell development. Thymi at most ages were small and their architecture was disorganized. This defect was not due to increased thymocyte apoptosis but to decreased cell proliferation. T cell development was found to be severely arrested at the CD4/CD8 double-negative 3 stage and the thymus contained very few double-positive or single-positive (SP) mature thymocytes. The mutant thymocytes showed impaired proliferative responses to anti-CD3 monoclonal antibody (mAb) stimulation or to the cytokines IL-2, IL-1 or TNF. In the spleen, the numbers of mature SP T cells were decreased and their proliferative responses to anti-CD3 plus IL-2 or to anti-CD28 mAb were impaired. A severe impairment of CD3-induced expression of CD25 was also observed. These data suggest that alpha4 plays a critical role in the proliferation of thymocytes, which is necessary for early T cell development. |
