Expression of Cutaneous Lymphocyte–Associated Antigen and E‐selectin Ligand by Circulating Human Memory CD4+T Lymphocytes Specific for Herpes Simplex Virus Type 2

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Abstract
Virus-specific memory T lymphocytes traffic to sites of viral infection. Herpes simplex virus (HSV) type 2-specific CD4+ and CD8+ T lymphocytes differ with regard to their homing kinetics to infected tissues. We studied the expression of cutaneous lymphocyte-associated antigen (CLA) and E-selectin ligand (ESL) by HSV-2-specific CD4+ T lymphocytes. Virus-reactive T lymphocytes were identified ex vivo by CD154 or interferon-γ up-regulation. We detected selective expression of CLA by HSV-2-reactive CD4+ T lymphocytes, but at levels lower than those we previously observed for CD8+ T lymphocytes. Short-term HSV-2-reactive CD4+ lines generated from peripheral-blood mononuclear cells preferentially express CLA, compared with cytomegalovirus- or influenza-specific cells. CLA is expressed by HSV-2-reactive cells that are initially CLA negative before restimulation. Short-term culture-expanded HSV-2-specific CD4+ T lymphocytes also selectively express ESL. These findings have implications for the optimization of vaccines for HSV and other cutaneous pathogens.