Transcription factor expression profiling to characterize differentiation of antigen-specific CD8 T cells induced by a live attenuated viral vaccine. (113.18)

Live attenuated SIV (SIVΔnef) is the most effective approach to induce protection to pathogenic SIV challenge in macaques. Protective immunity, in part mediated by CD8 T cell responses, correlates with phenotypic maturation of SIV-specific T cells, but remains incompletely understood. Expression profiling of T cell transcription factors (TF) offers a novel approach to characterize antigen-specific T cell differentiation. Highly parallel qRT-PCR was used to characterize the expression of 21 TF in naïve, central, transitional, and effector memory T cell subsets, and in SIV-specific CD8 T cells obtained at times associated with lesser protection (wk 5) and greater protection (wk 20) following SIVΔnef vaccination. Unsupervised clustering organized samples from CD4 and CD8 T cells into groups concordant with cell surface phenotype. TF expression in SIV-specific CD8+ T cells segregated by time, with wk 20 cells exhibiting increased expression of TF associated with both maintenance of quiescence (TCF7, BAZF) and promotion of effector function (Eomes, T-Bet). Different expression profiles were observed in T cells specific for different SIV epitopes, consistent with different epitope escape kinetics. TF expression profiling suggests T cell responses correlated with protection may include characteristics of both memory and effector cells. TF expression profiling can provide data complementary to the analysis of memory cell differentiation based on classical phenotypic markers.