The Journal of Experimental Medicine
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Published 4 March 2002. doi:10.1084/jem.20012023
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© Rockefeller University Press, 0022-1007/2002/3/651/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 5, March 4, 2002 651-656

Brief Definitive Report

Rapid Cytotoxic T Lymphocyte Activation Occurs in the Draining Lymph Nodes After Cutaneous Herpes Simplex Virus Infection as a Result of Early Antigen Presentation and Not the Presence of Virus

Scott N. Mueller1, Claerwen M. Jones1, Chris M. Smith2, William R. Heath2 and Francis R. Carbone1

1 Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, 3010, Australia
2 Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3050, Australia

Address correspondence to Francis R. Carbone, Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, 3010, Australia. Phone: 61-3-8344-9923; Fax: 61-3-9347-1540; E-mail: fcarbone{at}unimelb.edu.au and William R. Heath, Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3050, Australia. Phone: 61-3-9345-2482; Fax: 61-3-9347-0852; E-mail: heath{at}wehi.edu.au

Localized cutaneous herpes simplex virus type 1 (HSV-1) infection leads to arming and initial expansion of cytotoxic T lymphocytes (CTLs) in the draining popliteal lymph nodes (PLNs) followed by migration and further proliferation in the spleen. To accurately characterize the sequence of events involved in the activation and generation of anti-HSV CTLs, we used T cell receptor (TCR) transgenic mice specific for the immunodominant epitope from HSV glycoprotein B (gB498–505). We describe the detection of the initiation of antigen presentation in the draining lymph nodes by 4–6 h after infection with HSV-1. Analysis of CD69 up-regulation revealed activation of gB-specific CD8+ T cells by 6–8 h after infection. Furthermore, we show that T cell proliferation begins no sooner than 24 h after activation and is marked by the concurrent appearance of CTL activity in the PLNs. These events are not dependent on the presence of virus in the draining lymph nodes, and suggest a requirement for recruitment of professional antigen-presenting cells to the site of T cell activation. Consequently, we have defined the initiation of the CD8+ T cell–mediated response to cutaneous HSV-1 infection, demonstrating that the immune response to localized viral infection depends only on the appearance of cells presenting virus-derived antigen and commences with remarkable swiftness.

Key Words: CD8+ T lymphocyte • HSV • TCR transgenic mice • antigen presentation • CFSE


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