CD27 stimulation promotes the frequency of IL-7R expressing memory precursors and prevents IL-12 mediated loss of CD8+ T cell memory in the absence of CD4+ T cell help

摘要

Fully functional CD8⁺ T cell memory is highly dependent upon CD4⁺ T cell support. CD4⁺ T cells play a critical role in inducing the expression of CD70, the ligand for CD27, on dendritic cells. Here we demonstrate that CD27 stimulation during primary CD8⁺ T cell responses regulates the ability to mount secondary CD8⁺ T cell responses. CD27 stimulation during vaccinia and dendritic cell immunization controls the expression of the IL-7 receptor (CD127), which has been shown to be necessary for memory CD8⁺ T cell survival. Further, CD27 stimulation during primary CD8⁺ T cell responses to vaccinia virus restrained the late expression on memory precursor cells of cytokine receptors that support terminal differentiation. The formation of CD8⁺ T cell memory precursors and secondary CD8⁺ T cell responses were restored in the absence of CD27 costimulation when endogenous IL-12 was not available. Similarly, the lesion in CD8⁺ T cell memory that occurs in the absence ofCD4⁺ T cells did not occur in mice lacking IL-12. These data indicate that CD4⁺ T cell help and, by extension, CD27 stimulation supports CD8⁺ T cell memory by modulating the expression of cytokine receptors that influence the differentiation and survival of memory CD8⁺ T cells.