In vivo depletion of CD4⁺CD25⁺ regulatory T cells in cats

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• 作者：S. Rochelle Smithberg ; Jonathan E. Fogle ; Angela M. Mexas ; Stacie K. Reckling ; Susan M. Lankford ; Mary B. Tompkins ; Gregg A. Dean
• 关键词：Regulatory T cell ; FOXP3 ; Feline immunodeficiency virus ; Monoclonal antibody
• 刊名：Journal of Immunological Methods
• 出版年：2008
• 出版时间：1 January 2008
• 年：2008
• 卷：329
• 期：1-2
• 页码：81-91
• 全文大小：635 K

文摘

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.