Inflationary expansion and maintenance of an MHC class Ib-restricted response to polyomavirus infection differ in their dependence on CD4 T cell help and CD28 costimulation. (105.45)

Abstract

Abstract We recently identified a protective MHC class Ib-restricted CD8 T cell response to infection by mouse polyomavirus (PA Swanson et al. 2008. JEM 205). These CD8 T cells recognize a peptide corresponding to amino acids 139-147 of the VP2 capsid protein presented by the nonpolymorphic Q9 molecule. This Q9:VP2.139-specific CD8 T cell response exhibits inflationary kinetics in MHC class Ia-deficient mice - a gradual expansion in the first three months post-infection with minimal contraction thereafter. We previously demonstrated that Q9:VP2.139-specific CD8 T cells are dependent on antigen for their expansion, but not for their long-term maintenance (PA Swanson et al. 2009. JI 182). Here, we tested the hypothesis that the expansion and maintenance phases of the Q9:VP2.139-specific T cell response are also differentially dependent on CD4 T cell help and CD28 and CD40 ligand costimulation. Either in vivo CD4 cell depletion or CD28/CD40L costimulation blockade inhibited expansion of Q9:VP2.139-specific CD8 T cells. We further found that CD28 blockade alone was sufficient to impair this expansion. In contrast, CD4 cell depletion, but not CD28/CD40L blockade, during the maintenance phase resulted in a decline in frequency of Q9:VP2.139-specific CD8 T cells. These results indicate that the Q9:VP2.139-specific CD8 T cell response depends on CD4 T cell help and CD28 costimulation for its inflationary expansion, but only on CD4 T cell help for its maintenance.