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Publication : Rapid clearance of herpes simplex virus type 2 by CD8+ T cells requires high level expression of effector T cell functions.

First Author  Nelson MH Year  2011
Journal  J Reprod Immunol Volume  89
Issue  1 Pages  10-7
PubMed ID  21444117 Mgi Jnum  J:175956
Mgi Id  MGI:5287969 Doi  10.1016/j.jri.2011.01.013
Citation  Nelson MH, et al. (2011) Rapid clearance of herpes simplex virus type 2 by CD8+ T cells requires high level expression of effector T cell functions. J Reprod Immunol 89(1):10-7
abstractText  CD8(+) T cells are important for resolution of HSV-2 lesions from the female genital epithelium. It is uncertain whether optimal clearance of viruses such as HSV-2 that cause a limited, non-systemic infection solely requires expression of effector functions by infiltrating CD8(+) T lymphocytes, or if the clearance rate is reflective of the expression level of critical effector functions. To address this, CD8(+) T cells from normal OT-I mice or OT-I mice deficient in IFNgamma (IFNgamma(-/-)) or the IFNgamma receptor (IFNgammaR(-/-)) were activated in vitro in the presence of IFNgamma or IL-4 to generate a series of effector populations (Tc1 and Tc2-like respectively) that secreted different levels of IFNgamma and expressed different levels of HSV-specific cytolytic function. Compared with Tc1 cells, Tc2-like cells produced the type 2 cytokines IL-4 and IL-5, exhibited decreased IFNgamma secretion, diminished proliferation in vitro, and decreased antigen-specific cytolysis in vivo. Clearance of an ovalbumin-expressing HSV-2 strain (HSV-2 tk(-) OVA) by adoptively transferred Tc2-like cells was delayed relative to Tc1 cell recipients. Because donor Tc2-like cells proliferated in vivo and infiltrated the infected genital epithelium similar to Tc1 cells, the diminished virus clearance by Tc2-like effector cells correlated with reduced expression of critical effector functions. Together, these results suggest that high level expression of protective T cell functions by effector T cells is necessary for optimal clearance of HSV-2 from the genital epithelium. These results have important implications for vaccines designed to elicit CD8(+) T cells against viruses such as HSV-2 that infect the genital tract.
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