Differential Kinetics and Specificity of EBV-Specific CD4+ and CD8+ T Cells During Primary Infection

Abstract

The generation and maintenance of virus-specific CD4+ T cells in humans are not well understood. We used short in vitro stimulation assays followed by intracellular cytokine staining to characterize the timing, magnitude, and Ag specificity of CD4+ T cells over the course of primary EBV infection. Lytic and latent protein-specific CD4+ T cells were readily detected at presentation with acute infectious mononucleosis and declined rapidly thereafter. Responses to BZLF-1, BMLF-1, and Epstein-Barr nuclear Ag-3A were more commonly detected than responses to Epstein-Barr nuclear Ag-1. Concurrent analyses of BZLF-1-specific CD4+ and CD8+ T cells revealed differences in the expansion, specificity, and stability of CD4+ and CD8+ T cell-mediated responses over time. Peripheral blood EBV load directly correlated with the frequency of EBV-specific CD4+ T cell responses at presentation and over time, suggesting that EBV-specific CD4+ T cell responses are Ag-driven.