Expression of cutaneous lymphocyte-associated antigen by CD8(+) T cells specific for a skin-tropic virus.
Virus-specific CD8(+) T cells traffic to infected tissues to promote clearance of infection. We used herpes simplex virus type 2 (HSV-2) as a model system to investigate CD8(+) T cell trafficking to the skin in humans. Using human leukocyte antigen (HLA) class I tetramers, we observed that HSV-specific CD8(+) T cells in the peripheral blood expressed high levels of cutaneous lymphocyte-associated antigen (CLA). In contrast, CD8(+) T cells specific for non-skin-tropic herpesviruses lacked CLA expression. CLA-positive HSV-2-specific CD8(+) T cells had the characteristics of central memory cells, expressing CCR7, CD62L, and CD28, and they proliferated briskly in response to antigen. CLA is related to a functional E-selectin ligand, and both E-selectin and CLA-positive cells were detected in HSV-2-infected skin. HSV-2-specific T cells adhered to cells transfected with E-selectin. A higher proportion of HSV-specific CD8(+) T cells recovered from herpes lesions express CLA compared with blood, consistent with a role for CLA in skin homing. To our knowledge, this is the first report of expression of tissue-specific adhesion-associated molecules by virus-specific CD8(+) T cells. The evaluation of vaccines for skin and mucosal pathogens should include study of the induction of appropriate tissue-specific homing molecules.
Department of Medicine, Department of Laboratory Medicine, and. Department of Pathobiology, University of Washington, Seattle, Washington 98104, USA.
David M
DM
Koelle
Zhi
Z
Liu
Christopher M
CM
McClurkan
Max S
MS
Topp
Stanley R
SR
Riddell
Eric G
EG
Pamer
Andrew S
AS
Johnson
Anna
A
Wald
Lawrence
L
Corey
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D016466:CHO Cells; D002461:Cell Line, Transformed; D002465:Cell Movement; D002478:Cells, Cultured; D006224:Cricetinae; D006558:Herpes Genitalis / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D012867:Skin / Q000276:immunology* / Q000821:virology
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D008024:Ligands; D008562:Membrane Glycoproteins