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Effector CD4+ T lymphocytes resolve acute herpes simplex virus (HSV‐1) infection at both genital and neuronal sites
Author(s) -
Johnson Alison J.,
Chu ChinFun,
Milligan Gregg N.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.855.12
Subject(s) - biology , herpes simplex virus , adoptive cell transfer , immunology , cd8 , virology , virus , t cell , antigen , immune system
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.