Background Genital herpes, caused by herpes simplex virus (HSV), is a disease of increasing importance in the United States. Researchers are attempting to design a vaccine, but two recent high quality trials of prophylactic vaccines showed inadequate results. Cutaneous lymphocyte-associated antigen (CLA), linked with T-cell homing to the skin, is highly expressed on T cells infiltrating HSV lesions and on HSV-specific CD8+ T cells. The ability to induce expression of CLA on HSV-specific T cells may improve vaccine efficacy. In conjunction with TCR stimulation, cytokines interleukin (IL)-12 and type 1 interferon (IFN) appear to stimulate CLA expression. We hypothesize that blocking IL-12 and IFN-α receptor will reduce CLA expression on CD4+ HSV-specific memory T cells in immunocompetent patients.
Study Design and Methods After culturing CFSE-stained human PBMCs with UV killed HSV-1 or HSV-2 in the presence of absence of anti-IL-12, anti-IFN-αR, or control antibodies, CLA expression on HSV-reactive large, granular, CFSElow, CD4high cells was detected using flow cytometry.
Results Individually, neither anti-IFN-αR antibody or anti-IL-12 antibody significantly reduced CLA expression on CD4+ HSV-specific T cells. The combination of both antibodies, however, significantly reduced (p=0.002) CLA expression from 32.4% to 13.2% among individuals with a strong reaction to HSV.
Conclusion These preliminary data suggest IL-12 and type 1 IFN synergistically contribute to the expression of CLA on CD4+ HSV-specific T cells in vitro upon re-stimulation by recall antigen. These innate responses to HSV may also amplify the expression of skin-homing molecules during recurrent HSV infection in vitro.
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