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Lbachir BenMohamed, Arif A Khan, Ruchi Srivastava, Doran Spencer, Sumit Garg, Steven Wechsler, Anthony B Nesburn; Phenotypic and Functional Characterization of Herpes Simplex Virus Glycoprotein B Epitope-specific Effector and Memory CD8+ T Cells from Ocular Herpes Symptomatic and Asymptomatic Individuals. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4402.
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© ARVO (1962-2015); The Authors (2016-present)
Herpes Simplex Virus type 1 (HSV-1) glycoprotein B- (gB-) specific CD8+ T cells protect mice from herpes infection and disease. However, whether and which HSV-1 gB-specific CD8+ T cells play a key role in the “natural” protection seen in HSV-1 seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined.
In this study, we have dissected the phenotype and the function of HSV-1 gB-specific CD8+ T cells from HLA-A*02:01 positive, HSV-1 seropositive ASYMP 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 HSV-specific CD8+ TEM cells in protection against herpes and should be considered in the development of an effective vaccine.
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