title: Herpes virus entry mediator (HVEM) modulates proliferation and activation of regulatory T cells following HSV-1 infection.
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.
authors: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
authors: Shalini
authors: S
authors: Sharma
authors: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
authors: Naveen K
authors: NK
authors: Rajasagi
authors: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
authors: Tamara
authors: T
authors: Veiga-Parga
authors: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA. Electronic address: btr@utk.edu.
authors: Barry T
authors: BT
authors: Rouse
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology; D016849:Keratitis, Herpetic / Q000276:immunology / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000276:immunology* / Q000378:metabolism; D011991:Receptors, Virus / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D053586:Virus Internalization
chemical_list: D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506029:Tnfrsf14 protein, mouse
keywords: HSK; HSV-1; HVEM; Tregs; gD