Differential effects of blocking PD-1/PDL1 interaction in enhancing virus specific CD8 T cell response in young and aged mice (67.4)

Abstract

Abstract In this report, we compared the impact of blocking PD-1/PDL1 interaction to the virus specific CD8 T cell function in young and old C57BL/6 mice. Anti-PDL1 mAb treatment at the time of foot-pad HSV-1 infection to young C57BL/6 mice resulted in significantly increased proportion of SSIEFARL specific effector CD8 T cells in popliteal lymph node (PLN), spleen and PBMC. The frequency of IFN-γ, TNF-α and IL2, secreting SSIEFARL specific CD8 T cells was also increased in anti-PDL1 treated mice in comparison to isotype treated groups. An increased proportion of granzyme B expressing CD8 T cells were determined in PLN and spleen of anti-PDL1 treated mice. Interestingly, blocking of PD-1/PDL1 interaction at the time of CD8 T cell priming in young mice also improved the quality of HSV-1 specific memory CD8 T cell pool as noted by an enhanced recall response to SSIEFARL encoding vaccinia virus. On the contrary, blocking PD-1/PDL-1 interaction in aged mice increased SSIEFARL specific CD8 T cells only in PLN but not in spleen and PBMC. Moreover, frequency of effector molecules (IFN-γ, TNF-α, IL-2 and Granzyme B) expressing CD8 T cells did not change significantly in any of the collected tissues. Additionally, unlike in young mice, α-PDL1 treatment during priming failed to improve the quality of memory CD8 T cell response in aged mice. Taken together, we suggest that blocking of PD-1/PDL-1 interaction during priming enhance HSV-1 specific CD8 T cell response in young but not in aged mice.