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Anthony B Nesburn, Ruchi Srivastava, Arif Khan, Steven Wechsler, Lbachir BenMohamed; Increased Frequency of Herpes Simplex Virus-Specific Effector Memory CD26+CD8+ T Cells in HSV-Seropositive Ocular Herpes Asymptomatic Patients. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3318.
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© ARVO (1962-2015); The Authors (2016-present)
Herpes Simplex Virus type 1- (HSV-1-) specific CD8+ T cells protect mice from herpes infection and disease. However, the phenotype and function of human CD8+ T cells that are associated with the “natural” protection seen in HSV-1 seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remains to be determined. CD26, a T cell activation antigen, is a key modulator in immune response with known dipeptidyl peptidase IV (DPPIV (12); EC 18.104.22.168) activity in its extracellular domain. CD26 not only acts as a functional dipeptidyl peptidase IV, but also binds strongly to adenosine deaminase. Considerable evidence suggests that CD26 can deliver a potent co-stimulatory signal to T-cells. This signal transducing property appears to be a property of its extracellular domain. In addition, CD26 appears to be a functional collagen receptor that may aid activated T-cells in localizing to inflammation in tissues.
In this study, we compared the expression of CD26 on peripheral HSV-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 report: (i) increased frequencies of HSV-specific effector memory (CD45RAlowCCR7low) CD26+CD8+ T cells in ten sequentially studied HLA-A*02:01 positive and HSV-1-seropositive ASYMP individuals compared to SYMP patients; (ii) robust and polyfunctional effector HSV-specific CD26+CD8+ T cell responses, assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107a/b cytotoxic degranulation, and IFN-g; were detected in ASYMP individuals, (iii) CD26 expression on HSV-specific CD8+ T cells correlated inversely with cell activation; and (iv) CD26 expression on HSV-specific effector CD8+ T cells negatively correlated with PD1 expression (P=0.0015).
Our findings reveal a novel CD26-mediated mechanism that might be involved in protective HSV-specific CD8+ T cell responses in ASYMP individuals, which spontaneously controls herpetic disease, and should guide the development of an effective T-cell-based herpes vaccine.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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