PD-L1 blockade differentially increases Treg and CD8 T cell proliferative capacity depending on host viremia.

PBMC from HIV-infected individuals were stimulated with Gag peptides for 6 days in the presence of a PD-L1 blocking antibody or an isotype control antibody. Proliferation was determined by CFSE dilution (A) and alternatively by Ki67 staining (B and C). FC (fold change) in proliferation is calculated as the ratio between PD-L1 blockade conditions and isotype control conditions. Each symbol represents the result for one individual. In panels A and B, the dashed line (FC = 1) indicates no change due to PD-L1 blockade. The means of fold changes in proliferation are shown. (A) Given are the fold changes in the proliferation of Treg (including eTreg and rTreg) (black circles), CD4- (empty squares) and CD8- (empty triangles) T cell populations of different HIV-infected study groups as indicated. Significant differences in fold change of proliferation of Treg, CD4- and CD8- T cells among the 4 HIV study groups were determined using the Kruskal-Wallis test. Significant differences were found in the fold change of proliferation of Treg cells across the 4 HIV- study groups (*p <0.05) but not of CD4- and CD8- T cells. (B) Fold changes in proliferation of Treg, CD4- and CD8- T cell populations upon PD-L1 blockade were measured longitudinally in 7 individuals before and after >2 years of antiretroviral treatment (pre-cART and on-cART, respectively). Significant differences in fold change of proliferation between Treg, CD4- and CD8- T cells were determined by a Wilcoxon matched pairs test (*p <0.05; ns: non significant). (C) Ratio of the FC in proliferation of CD8 T cells and the FC in proliferation of Treg cells upon PD-L1 blockade. The dashed line (FC = 1) indicates the same FC in proliferation for CD8 T and Treg cells upon PD-L1 blockade. Significant differences between the ratios before and after antiretroviral treatment were determined by Wilcoxon matched pairs test (*p <0.05).