Cutting Edge: CD4+ T Cell Help Can Be Essential for Primary CD8+ T Cell Responses In Vivo

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Abstract
Recent studies have shown that CD4+ T cell help is required for the generation of memory CD8+ T cells that can proliferate and differentiate into effector cells on Ag restimulation. The importance of help for primary CD8+ T cell responses remains controversial. It has been suggested that help is not required for the initial proliferation and differentiation of CD8+ T cells in vivo and that classical models of helper-dependent responses describe impaired secondary responses to Ag in vitro. We have measured primary CD8+ T cell responses to peptide-pulsed dendritic cells in mice by cytokine ELISPOT and tetramer staining. No responses were detected in the absence of help, either when normal dendritic cells were injected into MHC II-deficient mice or when MHC II-deficient dendritic cells were injected into normal mice. Thus, the primary in vivo CD8+ T cell response depends absolutely on help from CD4+ T cells in our experimental system.