Dysfunctional Senescent Herpes Simplex Virus Specific CD57+CD8+ T cells are Associated with Recurrent Symptomatic Herpes in Humans | bioRxiv
Here we report that, HSV-specific CD8+ T cells from SYMP(recurrent herpes) patients, but not from ASYMP(asymptomatic) individuals, have phenotypic and functional characteristics of cellular senescence, including:
(i) high frequency of senescent (CD57+) and exhausted (PD-1+) CD8+ T cells;
(ii) late terminally differentiated (KLRG1+), non-proliferating CD8+ T cells
(iii) HSV-specific CD8+ T cells were declined overtime and were not maintained homeostatistically (CD127+CD8+ T cells);
(iv) loss of co-stimulatory molecule (CD28) on HSV-specific CD8+ T cells;
(v) decreased production of effector molecules (granzyme B and perforin) by HSV-specific CD8+ T cells.
Our findings provide insights into the role of senescence in HSV-specific CD8+ T cells in susceptibility to recurrent herpes and have implications for T-cell-based immunotherapeutic strategies against recurrent herpes in humans.