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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2019-10-01
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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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issn | 1999-4915 |
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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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