Teriflunomide inhibits activation-induced CD25 expression on T cells and may affect Foxp3-expressing regulatory T cells

• Published in: Research in veterinary science 2020-10, Vol.132, p.17-27
• Main Authors: Jasiecka-Mikołajczyk, Agnieszka, Socha, Piotr
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; CD25; CD25 antigen; CD4 antigen; CD4+ cells; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8+ cells; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell activation; Cell proliferation; Cloning; Crotonates - pharmacology; Dog; Dogs; Dogs - immunology; Drugs; Experiments; Flow cytometry; Forkhead protein; Forkhead Transcription Factors - metabolism; Foxp3; Foxp3 protein; Immunologic Factors - pharmacology; Immunomodulation; Immunoregulation; Interleukin 2; Interleukin 2 receptors; Interleukin-2 Receptor alpha Subunit - metabolism; Kinases; Lymphocytes; Lymphocytes T; Mode of action; Pathogenesis; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Teriflunomide; Toluidines - pharmacology; Veterinary medicine
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2020.05.011

Teriflunomide (TER) is an immunomodulatory agent. Although the first reports on the use of TER in dogs have already appeared, immune mechanisms underlying the immunomodulatory effect of TER do not seem to have been fully elucidated yet. There were two aspects of this study. First, further insight into the mode of action of TER was gained by investigating its effect on the expression of IL-2 receptor α-chain (CD25) and Forkhead box P3 (Foxp3) by CD4+ and CD8+ T cells and apoptosis of these cells. Second, in view in the earlier lack of data on the effect of TER on T cells in dogs, the results of this study filled in this gap. TER at a concentration which can be achieved in vivo prevented or reduced the activation-induced CD25 expression on CD4+ and CD8+ T cells, respectively. Taking into consideration the role of CD25 in T cell proliferation, this effect may constitute an additional mechanism responsible for the antiproliferative effect of the drug. Under stimulation conditions, TER induced Foxp3 expression in Foxp3-negative CD4+ and CD8+ T cells, while down-regulating it under unstimulated conditions. These results suggest that TER may generate iTreg cells, but this process requires cell activation. TER was not found to affect on the absolute count and apoptosis of CD4+ and CD8+ T cells. The results suggest that the impairment of CD25 expression during T cell activation and generation of iTreg cells may constitute additional mechanisms, besides the principal one, underlying the immunomodulatory effect of TER. •Teriflunomide reduces the activation-induced CD25 expression on canine T cells.•Teriflunomide induces Foxp3 expression in Foxp3-negative CD4+ and CD8+ T cells.•Teriflunomide does not affect the absolute count of total CD4+ and CD8+ T cells.•Teriflunomide has no effect on apoptosis of canine CD4+ and CD8+ T cells.•Teriflunomide may generate iTreg cells, but this process requires T cell activation.