CD28 provides T cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer. Export

@article{citeulike:2239985, abstract = {Activation of PI3K is among the earliest signaling events observed in T cells after conjugate formation with antigen presenting cells (APCs). The relevant PI3K catalytic isoform and relative contribution of the TcR and CD28 to PI3K activity at the immune synapse have not been determined unequivocally. Here we show, using a quantitative imaging-based assay, that the PI3K activity at the T cell - APC contact area is dependent on the p110delta but not the p110gamma, isoform of PI3K. CD28 enhanced PIP3 production at the T cell synapse independently of its YMNM PI3K-recruitment motif which instead was required for efficient PKC recruitment. CD28 could partially compensate for the lack of p110delta activity during T cell activation which indicates that CD28 and p110delta act in parallel and complementary pathways to activate T cells. Consistent with this, CD28 and p110delta double deficient mice were severely immune compromised. We therefore suggest that combined pharmaceutical targeting of p110delta activity and CD28 costimulation has potent therapeutic potential.}, address = {Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.}, author = {Garcon, Fabien and Patton, Daniel T T. and Emery, Juliet L L. and Hirsch, Emilio and Rottapel, Robert and Sasaki, Takehiko and Okkenhaug, Klaus}, citeulike-article-id = {2239985}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2007-08-108050}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18006698}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18006698}, day = {15}, doi = {10.1182/blood-2007-08-108050}, issn = {0006-4971}, journal = {Blood}, keywords = {cd28, p110delta, p110g}, month = {November}, posted-at = {2008-01-16 16:51:02}, priority = {0}, title = {CD28 provides T cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer.}, url = {http://dx.doi.org/10.1182/blood-2007-08-108050}, year = {2007} }

TY - JOUR ID - citeulike:2239985 L3 - citeulike-article-id:2239985 N2 - Activation of PI3K is among the earliest signaling events observed in T cells after conjugate formation with antigen presenting cells (APCs). The relevant PI3K catalytic isoform and relative contribution of the TcR and CD28 to PI3K activity at the immune synapse have not been determined unequivocally. Here we show, using a quantitative imaging-based assay, that the PI3K activity at the T cell - APC contact area is dependent on the p110delta but not the p110gamma, isoform of PI3K. CD28 enhanced PIP3 production at the T cell synapse independently of its YMNM PI3K-recruitment motif which instead was required for efficient PKC recruitment. CD28 could partially compensate for the lack of p110delta activity during T cell activation which indicates that CD28 and p110delta act in parallel and complementary pathways to activate T cells. Consistent with this, CD28 and p110delta double deficient mice were severely immune compromised. We therefore suggest that combined pharmaceutical targeting of p110delta activity and CD28 costimulation has potent therapeutic potential. JF - Blood SN - 0006-4971 AD - Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom. TI - CD28 provides T cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer. KW - cd28 KW - p110delta KW - p110g AU - Garcon, Fabien AU - Patton, Daniel T AU - Emery, Juliet L AU - Hirsch, Emilio AU - Rottapel, Robert AU - Sasaki, Takehiko AU - Okkenhaug, Klaus PY - 2007/11/15/ UR - http://dx.doi.org/10.1182/blood-2007-08-108050 ER -