Control of Lymphocyte Trafficking in HSV Infection

David Koelle, MD

As of Spring 2003, the lab is starting a five-year NIH-funded Project on how herpes simplex virus-specific T-cells home to sites of infection.   The discovery of HSV-2 CD8 and CD4 T-cell epitopes has allowed us to make fluorescent tetrameric reagents, which have in turn enabled the detection of HSV-2-specific T-cells in blood and lesion specimens, and the study of molecules involved in homing.   HSV-2 infects skin and mucous membranes.   We have found that cutaneous lymphoctye-associated antigen (CLA) is preferentially expressed by circulating, HSV-2-specific CD8 T-cells.   CMV and EBV do not cause skin lesions, and CD8 T-cells responding to these viruses do not over-express CLA.   The CLA on HSV-2-specific T-cells is functional, mediating binding to E-selectin.   These initial data implicate CLA in rolling adhesion of circulating HSV-2-specific PBMC to vascular endothelium.   However, there are unanswered questions concerning the chemokines and chemokine receptors involved in lymphocyte homing, the development of homing receptor expression during T-cell priming, and the molecules involved in CD4 and NK cell homing.   We plan to use mRNA measurement, immunocytochemistry, flow cytometry, and functional migration assays to address these issues.

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Publications:

Koelle DM , Liu Z, McClurkan CM, Topp M, Riddell SR, Pamer EG, Johnson AS, Wald A, Corey L.   2002.   Expression of cutaneous lymphocyte-associated antigen by CD8+ T cells specific for a skin-tropic virus.   Journal of Clinical Investigation 110: 537-548