Expression of cutaneous lymphocyte-associated antigen by CD8+ T cells specific for a skin-tropic virus

  • Koelle, David M.
  • Liu, Zhi
  • McClurkan, Christopher M.
  • Topp, Max S.
  • Riddell, Stanley R.
  • Pamer, Eric G.
  • Johnson, Andrew S.
  • Wald, Anna
  • Corey, Lawrence

  • 1Department of Medicine,

    2Department of Laboratory Medicine, and

    3Department of Pathobiology, University of Washington, Seattle, Washington, USA

    4Virginia Mason Research Center, Seattle, Washington, USA

    5Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    6Memorial Sloan Kettering Cancer Center, New York, New York, USA

    7Department of Epidemiology, University of Washington, Seattle, Washington, USA

See the related Commentary beginning on page 441.

Received for publication March 27, 2002, and accepted in revised form June 11, 2002.

Address correspondence to: David M. Koelle, Harborview Medical Center Mail Stop 359690, 325 Ninth Avenue, Seattle, Washington 98104, USA. Phone: (206) 341-5207; Fax: (206) 341-5203; E-mail: [email protected].

Conflict of interest: D.M. Koelle and L. Corey are co-inventors on patents covering the use of HSV-2 antigens as vaccines. The patents have been licensed to Corixa Inc. (Seattle, Washington, USA) by the University of Washington.

Nonstandard abbreviations used: cutaneous lymphocyte-associated antigen (CLA); herpes simplex virus type 2 (HSV-2); human leukocyte antigen (HLA); HSV-2 virion protein (VP); HSV-2-infected cell protein 0 (ICP0); cytomegalovirus (CMV); Epstein-Barr virus (EBV); EBV-transformed B cell (EBV-LCL); Chinese hamster ovary (CHO); phytohemagglutinin (PHA); amino acids (a.a.); phycoerythrin (PE); transporter associated with antigen processing (TAP).
Journal of Clinical Investigation 110(4):p 537-548, August 2002.

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.

Copyright © 2002 The American Society for Clinical Investigation, Inc.
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