Phosphatidylinositol 3 kinase activity is not essential for B7-1-mediated costimulation of proliferation or development of cytotoxicity in murine T cells.
It has been suggested that induction of phosphatidylinositol (PI) 3 kinase activity upon CD28 costimulation may contribute to CD28-mediated signaling. In this report, T cell stimulation by microspheres bearing coimmobilized anti-TCR mAb and purified B7-1 ligand was examined. This approach allows study of cosignaling mediated by CD28 interaction with its native ligand in the absence of potentially confounding contributions from other receptor-ligand interactions. For murine CD4+ and CD8+ T cells, costimulation with B7-1 up-regulated PI3 kinase activity assayed in vitro, and this was blocked by treatment of the cells with wortmannin, a specific inhibitor of PI3 kinase, before stimulation. However, wortmannin failed to inhibit B7-1-dependent T cell proliferation or development of cytotoxicity in CD8+ cells. These results indicate that the enzymatic activity of PI3 kinase is not essential in the CD28-mediated signaling involved in the costimulation of proliferation or induction of CTL activity in precursor CTL.
Ni
H T
HT
Center for Immunology, University of Minnesota, Minneapolis 55455, USA.
Deeths
M J
MJ
Mescher
M F
MF
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism* / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology* / Q000276:immunology*
D018122:B7-1 Antigen; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor)