Homing in on the cellular immune response to HSV-2 in humans.
OBJECTIVE
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.


METHODS
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.
Koelle
David M
DM
Department of Medicine, University of Washington, Seattle, WA 98104, USA. viralimm@u.washington.edu
Gonzalez
Julio C
JC
Johnson
Andrew S
AS
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019040:E-Selectin / Q000096:biosynthesis; D000939:Epitopes; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000473:pathology / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D036904:Leukocyte Rolling / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000821:virology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D019040:E-Selectin; D000939:Epitopes; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta