The role of PKC-Theta in CD8 T cell activation (B28)

Abstract

Abstract Protein kinase C- Theta (PKC𝛉) is known to be a key mediator of NF-κB activation downstream of TCR signaling. However, recent in vivo studies with PKC𝛉−/− mice have generated conflicting results regarding its role in T cell activation. To elucidate the role of PKC𝛉 in the activation of CD8 T cells, we generated ovalbumin (ova)-specific PKC𝛉−/− OT1 mice. Stimulation of PKC𝛉−/− OT1 CD8 T cells with microspheres coupled to H2Kb-ova demonstrated a critical function for PKC𝛉 in TCR-induced NF-κB activation and proliferation in vitro. In contrast, ova-induced proliferation and CTL generation in vivo was virtually the same as WT cells. In addition, PKC𝛉−/− CD8 T cells stimulated in vitro with ova-pulsed DC proliferated vigorously and to a similar extent as WT cells. Remarkably, comparable levels of NF-κB were activated in WT and PKC𝛉−/− T cells after stimulation with DC. Proliferation of PKC𝛉−/− cells is severely reduced when DC deficient for B7-1/2 are used to stimulate the cells. Costimulation provided by CD27L also plays a role, as demonstrated by the use of a specific blocking antibody. In contrast to the response against antigen, GVHD responses are severely impaired in the absence of PKC𝛉. These results suggest that impaired TCR/antigen-induced NF-κB activation in PKC𝛉−/− CD8 T cells does not have a significant impact on T cell proliferation when other non-TCR signaling pathways are able to induce NF-κB and T cell activation.