SC-46 Vδ2 T cells effector response in PLWH and PLWoH up to three months from mpox infection

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Background The first evidence that Orthopoxviruses induced the in vivo expansion and the recall of effector Vδ2 T-cells was described in a macaque model. Although, it was analysed an engagement of αβ T-cells specific response in patients infected with human monkeypox (mpox), little is known about the role of γδ T-cells during mpox infection. IFN-γ-producing γδ T-cells in innate resistance to poxviruses may play a key role in inducing a protective type 1 memory immunity by influencing the effectiveness of vaccines. In this study, we analysed the kinetics of Vδ2 T-cells from symptoms onset (FSO) up to three months after mpox infection. Material and Methods 9 MSM subjects, with confirmed mpox, were enrolled in a longitudinal study from May to July 2022, and blood samples collected in the early phase of infection (T1, T2) and at 3 months (T3M) FSO. Four were PLWH, all on ART with good viro-immunological status (CD4 count median: 653). Vδ2 T-cells profile (CD45RA/CCR7), activation/exhaustion markers expression (CD38/HLA-DR/CD57/PD-1/TIM-3), cytokines production (IFNγ/TNFα) and CD107a expression after non-peptidic antigen stimulation, were assessed by multiparametric flow cytometry. Kinetics of Vδ2 T-cell response were compared with 13 healthy donors (HD) matched by sex and age. Mann-Whitney and Wilcoxon tests were used for statistics. Results At T1, Vδ2 T-cells frequency was lower than HD (p<0.01, figure 1 panel A); in addition, an expansion of Effector Memory Vδ2 T-cells was observed (p<0.002, figure 1 panel B), paralleled to a decrease of Central Memory Vδ2 T-cells (p<0.0001, figure 1 panel B), reaching HD values after T3M FSO. Activation/exhaustion markers were significantly increased at T1 (figure 1 panels C-G) and resulted lower after T3M. HLA-DR expression was higher in PLWH than PLWoH. No differences were observed for the other markers according to PLWH/PLWoH stratification. Vδ2 functionality decreased at T1 when compared to HD (figure 1 panels H-L), and it was associated with a CD38 higher expression (p<0.02, figure 1 panel M). At T3M, Vδ2 T-cells response was restored and seems linked to TIM-3 expression (p<0.009, figure 1 panel O). Conclusions The presence of effector/activated Vδ2 T-cells in the early stages of infection and their capability to activate quickly, producing pro-inflammatory cytokines may be useful to enhance the early adaptive response to human mpox for the maintenance of the protective memory/effector T-cells response.

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