Herpes simplex virus type 1 glycoprotein B-specific effector memory CD8+ T cells are associated with asymptomatic ocular herpes disease in both humans and "humanized" HLA transgenic mice (HUM6P.245)

Abstract

Abstract We have dissected the phenotype and the function of HSV-1 glycoprotein B- (gB-) specific CD8+ T cells from HLA-A*02:01 positive, HSV-1 seropositive asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) and symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpes disease). We found that: (i) healthy ASYMP individuals maintained a significantly higher proportion of differentiated HSV-1 gB-specific effector memory CD8+ T cells (TEM, CD45RAlowCCR7lowCD44highCD62Llow). In contrast, SYMP patients had frequent less-differentiated central memory CD8+ T cells (TCM, CD45RAlowCCR7highCD44lowCD62Lhigh); (ii) ASYMP individuals had significantly higher proportions of multi-functional effector CD8+ T cells, which responded mainly to gB342-350 and gB561-569 “ASYMP” epitopes, and simultaneously produced IFN-g, CD107a/b, granzyme B and perforin. In contrast, effector CD8+ T cells from SYMP individuals were mostly mono-functional and were directed mainly against non-overlapping gB17-25 and gB183-191 “SYMP” epitopes; (iii) immunization of HLA-A*02:01 transgenic mouse model of ocular herpes with “ASYMP” CD8+ TEM cell epitopes, but not with “SYMP” CD8+ TCM cell epitopes, induced a strong CD8+ T cell-dependent protective immunity against ocular herpes infection and disease. Our findings provide insights into the role of CD8+ TEM cells in protection against herpes and should be considered in the development of an effective vaccine.