| First Author | Selvaraj RK | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 5 | Pages | 2830-8 |
| PubMed ID | 18292504 | Mgi Jnum | J:131562 |
| Mgi Id | MGI:3773965 | Doi | 10.4049/jimmunol.180.5.2830 |
| Citation | Selvaraj RK, et al. (2008) Mitigation of Experimental Allergic Encephalomyelitis by TGF-{beta} Induced Foxp3+ Regulatory T Lymphocytes through the Induction of Anergy and Infectious Tolerance. J Immunol 180(5):2830-2838 |
| abstractText | Stimulation of naive T lymphocytes in the presence of IL-2 and TGF-beta induces the regulatory transcription factor Foxp3, which endows the cells with regulatory functions. To better understand the properties and therapeutic potential of these induced regulatory T cells (iTreg), we examined their immunomodulatory properties in myelin oligodendroglial glycoprotein-induced experimental allergic encephalomyelitis (MOG-EAE). Adoptively transferred iTreg were as potent as natural Foxp3(+) Treg in preventing EAE development, and were active both prophylactically and after priming. The iTreg migrated into the CNS in quantity, skewing the ratio of regulatory to effector T lymphocytes. IL-10(-/-) iTreg failed to suppress disease, demonstrating a critical role for iTreg IL-10 production in their therapeutic activity. MOG-specific T cells from iTreg treated animals were anergic. The cells failed to proliferate in response to Ag except in the presence of exogenous IL-2, and did not secrete or secreted reduced amounts of IL-2, IFN-gamma, and IL-17. MOG-specific T cells were not wholly unresponsive though, as they did secrete IL-10 after stimulation. To determine whether iTreg-mediated tolerance was infectious, fostering the development of T lymphocytes that could independently suppress EAE, we purged draining lymph node cells from MOG-immunized, iTreg treated mice of the administered iTreg, and transferred the remaining cells to Ag-inexperienced mice. The transferred cells were able to block EAE development. Thus iTreg are highly potent suppressors of autoimmune encephalomyelitis, and act in an IL-10 dependent manner both through the induction of anergy in effector T cells and through the infectious induction of protective T lymphocytes able to independently suppress disease development. |
