Effects of Regulatory T Cell Depletion on NK Cell Responses against <i>Listeria monocytogenes</i> in Feline Immunodeficiency Virus Infected Cats

Regulatory T cells (Treg) are key players in the maintenance of peripheral tolerance, preventing autoimmune diseases and restraining chronic inflammatory diseases. Evidence suggests Treg cells and NK cells have important roles in feline immunodeficiency virus (FIV) pathogenesis; however, in vivo stu...

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Main Authors: Rita D. Simões, Alora LaVoy, Gregg A. Dean
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/11/11/984
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author Rita D. Simões
Alora LaVoy
Gregg A. Dean
author_facet Rita D. Simões
Alora LaVoy
Gregg A. Dean
author_sort Rita D. Simões
collection DOAJ
description Regulatory T cells (Treg) are key players in the maintenance of peripheral tolerance, preventing autoimmune diseases and restraining chronic inflammatory diseases. Evidence suggests Treg cells and NK cells have important roles in feline immunodeficiency virus (FIV) pathogenesis; however, in vivo studies investigating the interplay between these two cell populations are lacking. We previously described innate immune defects in FIV-infected cats characterized by cytokine deficits and impaired natural killer cell (NK) and NK T cell (NKT) functions. In this study, we investigated whether in vivo Treg depletion by treatment with an anti-feline CD25 monoclonal antibody would improve the innate immune response against subcutaneous challenge with <i>Listeria monocytogenes</i> (Lm). Treg depletion resulted in an increased overall number of cells in Lm-draining lymph nodes and increased proliferation of NK and NKT cells in FIV-infected cats. Treg depletion did not normalize expression of perforin or granzyme A by NK and NKT cells, nor did Treg depletion result in improved clearance of Lm. Thus, despite the quantitative improvements in the NK and NKT cell responses to Lm, there was no functional improvement in the early control of Lm. CD1a+ dendritic cell percentages in the lymph nodes of FIV-infected cats were lower than in specific-pathogen-free control cats and failed to upregulate CD80 even when Treg were depleted. Taken together, Treg depletion failed to improve the innate immune response of FIV-infected cats against Lm and this may be due to dendritic cell dysfunction.
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spelling doaj.art-e475513806234a11b57bddc266e9c3652022-12-21T23:35:26ZengMDPI AGViruses1999-49152019-10-01111198410.3390/v11110984v11110984Effects of Regulatory T Cell Depletion on NK Cell Responses against <i>Listeria monocytogenes</i> in Feline Immunodeficiency Virus Infected CatsRita D. Simões0Alora LaVoy1Gregg A. Dean2Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USACenter for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USACenter for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USARegulatory T cells (Treg) are key players in the maintenance of peripheral tolerance, preventing autoimmune diseases and restraining chronic inflammatory diseases. Evidence suggests Treg cells and NK cells have important roles in feline immunodeficiency virus (FIV) pathogenesis; however, in vivo studies investigating the interplay between these two cell populations are lacking. We previously described innate immune defects in FIV-infected cats characterized by cytokine deficits and impaired natural killer cell (NK) and NK T cell (NKT) functions. In this study, we investigated whether in vivo Treg depletion by treatment with an anti-feline CD25 monoclonal antibody would improve the innate immune response against subcutaneous challenge with <i>Listeria monocytogenes</i> (Lm). Treg depletion resulted in an increased overall number of cells in Lm-draining lymph nodes and increased proliferation of NK and NKT cells in FIV-infected cats. Treg depletion did not normalize expression of perforin or granzyme A by NK and NKT cells, nor did Treg depletion result in improved clearance of Lm. Thus, despite the quantitative improvements in the NK and NKT cell responses to Lm, there was no functional improvement in the early control of Lm. CD1a+ dendritic cell percentages in the lymph nodes of FIV-infected cats were lower than in specific-pathogen-free control cats and failed to upregulate CD80 even when Treg were depleted. Taken together, Treg depletion failed to improve the innate immune response of FIV-infected cats against Lm and this may be due to dendritic cell dysfunction.https://www.mdpi.com/1999-4915/11/11/984feline immunodeficiency virusnk cellsregulatory t cellsinnate immunitytreg depletion
spellingShingle Rita D. Simões
Alora LaVoy
Gregg A. Dean
Effects of Regulatory T Cell Depletion on NK Cell Responses against <i>Listeria monocytogenes</i> in Feline Immunodeficiency Virus Infected Cats
Viruses
feline immunodeficiency virus
nk cells
regulatory t cells
innate immunity
treg depletion
title Effects of Regulatory T Cell Depletion on NK Cell Responses against <i>Listeria monocytogenes</i> in Feline Immunodeficiency Virus Infected Cats
title_full Effects of Regulatory T Cell Depletion on NK Cell Responses against <i>Listeria monocytogenes</i> in Feline Immunodeficiency Virus Infected Cats
title_fullStr Effects of Regulatory T Cell Depletion on NK Cell Responses against <i>Listeria monocytogenes</i> in Feline Immunodeficiency Virus Infected Cats
title_full_unstemmed Effects of Regulatory T Cell Depletion on NK Cell Responses against <i>Listeria monocytogenes</i> in Feline Immunodeficiency Virus Infected Cats
title_short Effects of Regulatory T Cell Depletion on NK Cell Responses against <i>Listeria monocytogenes</i> in Feline Immunodeficiency Virus Infected Cats
title_sort effects of regulatory t cell depletion on nk cell responses against i listeria monocytogenes i in feline immunodeficiency virus infected cats
topic feline immunodeficiency virus
nk cells
regulatory t cells
innate immunity
treg depletion
url https://www.mdpi.com/1999-4915/11/11/984
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