Methods: The study used peripheral blood mononuclear cells (PBMC) cryopreserved at mean (SD) of 2.7 (2.5) months before HZ from 31 PLWH cases on ART with plasma vRNA <200 c/mL, and CD4 counts ≥200 cells/µL. 31 non-HZ controls were matched to cases by CD4 count, age, sex, race, parent study, and ART duration. T cell subsets were measured by flow cytometry after ex vivo VZV- and mock-restimulation and in freshly thawed unstimulated PBMC using the following markers: CD3, CD8, CD25, CD28, CD39, CD57, CD127, CTLA4, FOXP3, IFNg, IL10, KLRG1, LAG3, PD1, perforin, TGFb, TIM3 and TNFa. Data were analyzed by paired t-tests.
Results: At PBMC collection, PLWH had mean (SD) age 41 (10) years; 16 females; 28 White and 22 Black Non-Hispanics; mean (SD) CD4 counts 501 (222) cells/µL; 56 (90%) vRNA <50 c/mL; median ART duration 50 weeks. In unstimulated PBMC, HZ cases had higher %FOXP3+CD25+(CD4+) Treg compared to controls (p=0.08). Cases generally had lower responses to ex vivo VZV-restimulation (after subtraction of mock) compared to controls, including %perforin+(CD8+) CTL (p=0.07) and %IL10+(CD4+) (p=0.04) and %TGFb+(CD4+) Treg (p=0.07). %FOXP3+CD25+(CD4+) Treg in unstimulated PBMC did not correlate with VZV-specific %perforin+(CD8+) or %IFNg+(CD4+) effector T cells, but the VZV-specific effector T cell percentages correlated with each other (r=0.24, p=0.05).
Conclusion: Although limited by small numbers, this study showed that before development of HZ, PLWH had marginally increased number of Treg in blood and decreased VZV-specific responses. VZV-specific Treg and CTL were equally lower in cases compared with controls, suggesting that a general low VZV-specific T cell responsiveness precedes HZ in PLWH. The lack of association between circulating Treg and VZV-specific T cell responses suggests independent mechanisms of action.
H. Chen, None
R. Bosch, None
A. Weinberg, None