Journal
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
Volume 53, Issue 4, Pages 172-181Publisher
WILEY
DOI: 10.1111/j.1600-0897.2005.00262.x
Keywords
cutaneous lymphocyte-associated antigen; E-selectin; herpes simplex virus; lymphocyte trafficking
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Funding
- NIAID NIH HHS [R01 AI050132, AI50132, P01 AI030731, AI30731] Funding Source: Medline
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PROBLEM: Genital herpes simplex infections are generally limited to epithelia and neurons. Vaccines have had activity in herpes simplex virus (HSV)-seronegative women only. Understanding how HSV-specific T cells traffic to infected sites may assist in vaccine design. METHOD OF STUDY: Herpes simplex virus epitopes recognized by HSV-specific CD8 T cells were identified and used to make fluorescent human leukocyte antigen (HLA)-peptide tetramers. Molecules related to lymphocyte rolling adhesion were studied by flow cytometry and cell binding. HSV-specific CD4 T cells identified ex vivo by cytokine accumulation or activation marker expression, or detected in vitro by 5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester (CFSE) dilution, were similarly investigated. RESULTS: Herpes simplex virus-specific T cells are 10- to 100-fold more prevalent in lesional skin compared with blood and greatly enriched in lesions compared with normal skin. Diverse viral antigens are recognized by HSV-specific T cells. Functionally active E-selectin ligand, and cutaneous lymphocyte antigen (CLA), are expressed by circulating HSV-2-specific CD8 cells. CD4 cells display lower levels of CLA that are dramatically up-regulated upon re-stimulation with antigen. CONCLUSIONS: Herpes simplex virus-2-specific CD8 and CD4 T cells differ in constitutive expression of skin homing molecules. Vaccines designed to induce proper homing are postulated to have increased efficacy.
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