Herpes virus entry mediator (HVEM) modulates proliferation and activation of regulatory T cells following HSV-1 infection |
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Institution: | 1. Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98115, USA;1. Department of Haematology, Cambridge Institute for Medical Research, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0XY, UK;1. National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India;2. Department of Veterinary Physiology and Biochemistry, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, India;3. Department of Veterinary Public Health and Epidemiology, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, India;1. Department of Veterinary Physiology and Biochemistry, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, 125004, Haryana, India;2. Department of Bio-technology, GLA University, Post-Chaumuhan, Dist., Mathura, Uttar Pradesh, 281 406, India;3. Department of Veterinary Clinical Complex, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, 125004, Haryana, India;1. University of Utah School of Medicine |
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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. |
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Keywords: | HSV-1 Tregs HSK HVEM gD |
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