June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
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
Author Affiliations & Notes
  • Lbachir BenMohamed
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, CA
  • Arif A Khan
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, CA
  • Ruchi Srivastava
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, CA
  • Doran Spencer
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, CA
  • Sumit Garg
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, CA
  • Steven Wechsler
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, CA
  • Anthony B Nesburn
    Gavin Herbert Eye Institute, Univ of California-Irvine, Irvine, CA
  • Footnotes
    Commercial Relationships Lbachir BenMohamed, None; Arif Khan, None; Ruchi Srivastava, None; Doran Spencer, None; Sumit Garg, None; Steven Wechsler, None; Anthony Nesburn, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4402. doi:
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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)

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Abstract

Purpose: 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.

Methods: 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).

Results: 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.

Conclusions: 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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