Effector CD4+ T lymphocytes resolve acute herpes simplex virus (HSV‐1) infection at both genital and neuronal sites

Abstract

In primary infection, CD8+ T cells are important for clearance of infectious HSV from sensory ganglia. We present evidence for CD4+ T cell‐mediated clearance of infectious HSV‐1 from genital tract and neuronal tissues. HSV‐specific CD4+ T cells were present in genital and neuronal tissues coincident with HSV‐1 clearance. Neuronal CD4+ T cells secreted IFN‐γ, TNF‐α, IL‐2 or IL‐4 after stimulation with HSV antigen. By adoptively transferring CD4+ T cells to Rag1−/ − mice, we showed that CD4+ T cells were sufficient for clearance of HSV‐1 from the genital tract. Compared to controls that did not receive T cells, CD4‐recipient mice had dramatically lower viral titers in the spinal cord and sensory ganglia, suggesting CD4+ T cells were active in clearing infectious HSV‐1 from neuronal tissue. To examine possible mechanisms by which CD4+ T cells resolve the neuronal HSV‐1 infection, CD4+ T cells from either perforin‐ or FasL‐deficient mice were adoptively transferred to Rag1−/ − mice. Clearance of infectious virus from genital and neuronal tissues was not significantly different in mice receiving these deficient T cells, compared to mice receiving wild‐type cells. These results suggest CD4+ T cells are important for resolution of primary HSV‐1 infection at both genital and neuronal sites, possibly via a non‐lytic mechanism. Supported by NIH grants AI42815, AI054444. Vale‐Asche Predoctoral Fellowship to AJJ.