Abstract
In many infections, especially those that are chronic such as Herpes Simplex Virus-1 (HSV-1), the outcome may be influenced by the activity of one or more types of regulatory T cells (Tregs). Some infections can cause Treg expansion, but how viruses might promote preferential Treg expansion is has been unclear. In this report, we demonstrate a possible mechanism by which HSV (Herpes Simplex virus-1) infection could act to signal and expands the Treg population. We show that CD4(+) FoxP3(+) Tregs up- regulate HVEM (herpes virus entry mediator), which is a binding site for major viral glycoprotein HSVgD, following HSV infection, which is a binding site for major viral glycoprotein HSVgD. Recombinant HSVgD enhanced the proliferation of CD4(+) FoxP3(+) Tregs cells in-vitro. Furthermore, compared to wild type (WT), HVEM deficient mice (HVEM-/-) generated a weaker Treg responses represented by significantly diminished ratios of CD4(+)FoxP3(+)/CD4(+)FoxP3(-) cells along with diminished proportions of FoxP3(+) Tregscells co-expressing Treg activation markers and a reduced MFI of FoxP3 expression on CD4(+) T cells. Consistent with defective Treg responses, HVEM-/- animals were more susceptible to HSV-1 induced ocular immunopathology, with more severe lesions in HVEM-/- animals. Our results indicate that HVEM regulates Treg responses, and its modulation could represent a useful approach to control HSV induced corneal immunopathology.