Antigen-specific precursor frequencies influence requirement of CD4+ T cell help and CD40-40L costimulation in primary and secondary responses (132.8)

Abstract

Abstract CD4+ T cells play a decisive role in generation of effective CD8+ T cell-mediated immunity against diseases associated with minor H antigens, including cancer, auto-immunity and allogenic tissue transplantation. The increased precursor frequency in reducing the need of CD4+ T cell help and costimulations in CD8+ T cell primary responses have been demonstrated. However, its similar roles in memory CD8+ T cell responses have not been fully understood. In a non-infectious vaccine model, here we show that, at endogenous precursor levels, CD4+ T cell help, and CD40-40L costimulation are required for both primary and memory responses. At increased precursor frequency, although CD4+ T cell help, and CD40-40L costimulation are not obligatory in primary responses, their requirement is still necessary for functional memory responses. Despite increased precursor frequency is ensured during priming, the memory CD8+ T cells developed from increased precursor frequency in the absence of CD4+ T cell help, and CD40-40L costimulation fail to induce complete protection following tumor challenge. These results further support the previous observations that efficient memory CD8+ T cell responses require CD4+ T cell help and CD40-40L costimulation.