Effect of PD-1-deficiency on the development of CD8 T cell response for a minor histocompatibility antigen, H60

Abstract

Activated CD8 T cells go through robust expansion and then a certain portion of the expanded CD8 T cells remain as memory cells after antigen is cleared. It has been well known that help from concomittantly activated CD4 T cells is essential for generation of memory CD8 T cells and the CD8 T cells activated in the absence of CD4 help show defect in memory expansion when re-exposured to the same antigen. PD-1 (programmed cell death-1

CD279), which is an inhibitory receptor up-regulated on activated T cells, has been suggested to be implicated in the memory generation of CD8 T cells. In this study, using a minor histocompatibility antigen H60 as a model antigen, for which specific primary and memory CD8 T cell expansion is heavily dependent on CD4 help, the impact of the presence and absence of PD-1-expression on the development of antigen-specific CD8 T cell response was investigated. In the absence of PD-1 expression, the H60-specific CD8 T cells underwent higher degree of proliferation and showed enhanced functionality including cytotoxicity for antigen clearance, compared to those with PD-1 expression, even under help-deficient condition. However, PD-1-deficiency did not restore central memory cell generation of CD8 T cells under help-deficient condition. These results suggest that role of PD-1 is not directly related to programming of memory CD8 T cell generation, but rather to enhancing effector function of activated CD8 T cells. The results from this study will provide insight into development of CD8 T cell response and memory generation.