In vivo depletion of CD4+CD25+ regulatory T cells in cats.
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.
Smithberg
S Rochelle
SR
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.
Fogle
Jonathan E
JE
Mexas
Angela M
AM
Reckling
Stacie K
SK
Lankford
Susan M
SM
Tompkins
Mary B
MB
Dean
Gregg A
GA
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
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