CD4+ helper T （Th） cells play pivotal roles in induction of CD8+ CTL immunity. However, the mechanism of CD4+ T cell help delivery to CD8+ T cells in vivo is still elusive. In this study, we used ovalbumin （OVA）-pulsed dendritic cells （DCOVA） to activate OT-II mouse CD4+ T cells, and then studied the help effect of these CD4+ T cells on CD8+ cytotoxic T lymphocyte （CTL） responses. We also examined CTL mediated islet β cell destruction which led to diabetes in wild-type C57BL/6 mice and transgenic rat insulin promoter （RIP）-mOVA mice expressing β cell antigen OVA with self OVA-specific tolerance, respectively. In adoptive transfer experiments, we demonstrated that help, in the form of peptide/major histocompatibility complex （pMHC） I acquired from DCOVA by DCOVA activation, was required for induction of OVA-specific CTL responses in C57BL/6 mice. However, in combination with TCR transgenic OT-I mouse CD8+ T cells, the tolerogenic dosage of CD4+ Th cells with acquired pMHC I, but not CD4+ （Kb-/-） Th cells without acquired pMHC I were able to cause diabetes in 8/10 （80%） RIP-mOVA mice. This study thus expands the current knowledge in T cell-mediated autoimmunity and provides insight into the nature of CD4+ T cell-mediated help in CD8+ CTL induction.
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