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Homing in on the Cellular Immune Response to HSV-2 in Humans*


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    Based in part on a presentation at the 23rd Annual Meeting of the American Society for Reproductive Immunology, St Louis, MO, June 2004.

Address reprints requests to David M. Koelle, MD, Department of Medicine, Harborview Medical Center Mail Stop 359690, 325 Ninth Avenue, Seattle, WA 98104, USA.


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.