title: In vivo depletion of CD4+CD25+ regulatory T cells in cats.
abstract: To establish a characterized model of regulatory T cell (Treg) depletion in the cat we assessed the kinetics of depletion and rebound in peripheral and central lymphoid compartments after treatment with anti-CD25 antibody as determined by cell surface markers and FOXP3 mRNA expression. An 82% decrease in circulating CD4+CD25+ Tregs was observed by day 11 after treatment. CD4+CD25+ cells were also reduced in the thymus (69%), secondary lymphoid tissues (66%), and gut (67%). Although CD4+CD25+ cells rebound by day 35 post-treatment, FOXP3 levels remain depressed suggesting anti-CD25 antibody treatment has a sustainable diminutive effect on the Treg population. To determine whether CD25+ Treg depletion strategies also deplete activated CD25+ effector cells, cats were immunized with feline immunodeficiency virus (FIV) p24-GST recombinant protein, allowing them to develop a measurable memory response, prior to depletion with anti-CD25 antibody. Anti-FIV p24-GST effector cell activity in peripheral blood after depletion was sustained as determined by antigen-specific T cell proliferation and humoral responses against FIV p24-GST with an ELISA for antigen-specific feline IgG. Furthermore, development of an anti-mouse response in Treg-depleted cats was similar to control levels indicating the retained capacity to respond to a novel antigen. We conclude that despite alterations in CD25+ cell levels during depletion, the feline immune system remains functional. We demonstrate here a model for the study of disease pathogenesis in the context of reduced numbers of immunosuppressive CD4+CD25+ Tregs throughout the feline immune system.
authors.affiliation: Center for Comparative Medicine and Translational Research and Department of Molecular Biomedical Sciences, 4700 Hillsborough Street, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
authors.forename: S Rochelle
authors.initials: SR
authors.lastname: Smithberg
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Fogle
authors.forename: Angela M
authors.initials: AM
authors.lastname: Mexas
authors.forename: Stacie K
authors.initials: SK
authors.lastname: Reckling
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lankford
authors.forename: Mary B
authors.initials: MB
authors.lastname: Tompkins
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Dean
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002415:Cats; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015683:Gene Products, gag / Q000494:pharmacology; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015683:Gene Products, gag; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D011994:Recombinant Proteins; C074662:p24 protein, Feline immunodeficiency virus