| First Author | Maltzman JS | Year | 2005 |
| Journal | J Exp Med | Volume | 202 |
| Issue | 7 | Pages | 893-900 |
| PubMed ID | 16186188 | Mgi Jnum | J:107467 |
| Mgi Id | MGI:3621257 | Doi | 10.1084/jem.20051128 |
| Citation | Maltzman JS, et al. (2005) Conditional deletion reveals a cell-autonomous requirement of SLP-76 for thymocyte selection. J Exp Med 202(7):893-900 |
| abstractText | The SH2 domain containing leukocyte phosphoprotein of 76 kD (SLP-76) is critical for pre-TCR-mediated maturation to the CD4+CD8+ double positive (DP) stage in the thymus. The absolute block in SLP-76null mice at the CD4-CD8-CD44-CD25+ (double-negative 3, DN3) stage has hindered our understanding of the role of this adaptor in alphabeta TCR-mediated signal transduction in primary thymocytes and peripheral T lymphocytes. To evaluate the requirements for SLP-76 in these events, we used a cre-loxP approach to generate mice that conditionally delete SLP-76 after the DN3 checkpoint. These mice develop DP thymocytes that express the alphabeta TCR on the surface, but lack SLP-76 at the genomic DNA and protein levels. The DP compartment has reduced cellularity in young mice and fails to undergo positive selection to CD4+ or CD8+ single positive (SP) cells in vivo or activation-induced cell death in vitro. A small number of CD4+SP thymocytes are generated, but these cells fail to flux calcium in response to an alphabeta TCR-generated signal. Peripheral T cells are reduced in number, lack SLP-76 protein, and have an abnormal surface phenotype. These studies show for the first time that SLP-76 is required for signal transduction through the mature alphabeta TCR in primary cells of the T lineage. |
