Conditional deletion reveals a cell-autonomous requirement of SLP-76 for thymocyte selection Export

@article{citeulike:6044807, abstract = {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{alpha} {beta} 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{alpha} {beta} 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{alpha} {beta} 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{alpha} {beta} TCR in primary cells of the T lineage. 10.1084/jem.20051128}, author = {Maltzman, Jonathan S. and Kovoor, Lisa and Clements, James L. and Koretzky, Gary A.}, citeulike-article-id = {6044807}, citeulike-linkout-0 = {http://dx.doi.org/10.1084/jem.20051128}, citeulike-linkout-1 = {http://jem.rupress.org/content/202/7/893.abstract}, citeulike-linkout-2 = {http://jem.rupress.org/content/202/7/893.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/16186188}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=16186188}, day = {3}, doi = {10.1084/jem.20051128}, journal = {J. Exp. Med.}, keywords = {knockout, slp-76, thymus}, month = {October}, number = {7}, pages = {893--900}, posted-at = {2009-10-30 20:55:05}, priority = {2}, title = {Conditional deletion reveals a cell-autonomous requirement of SLP-76 for thymocyte selection}, url = {http://dx.doi.org/10.1084/jem.20051128}, volume = {202}, year = {2005} }

TY - JOUR ID - citeulike:6044807 L3 - citeulike-article-id:6044807 N2 - 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{alpha} {beta} 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{alpha} {beta} 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{alpha} {beta} 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{alpha} {beta} TCR in primary cells of the T lineage. 10.1084/jem.20051128 IS - 7 JF - J. Exp. Med. EP - 900 TI - Conditional deletion reveals a cell-autonomous requirement of SLP-76 for thymocyte selection VL - 202 SP - 893 KW - knockout KW - slp-76 KW - thymus AU - Maltzman, Jonathan AU - Kovoor, Lisa AU - Clements, James AU - Koretzky, Gary PY - 2005/10/03/ UR - http://dx.doi.org/10.1084/jem.20051128 ER -