| First Author | Kim YH | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 3 | Pages | 1120-8 |
| PubMed ID | 21715692 | Mgi Jnum | J:179178 |
| Mgi Id | MGI:5301235 | Doi | 10.4049/jimmunol.1002681 |
| Citation | Kim YH, et al. (2011) 4-1BB triggering ameliorates experimental autoimmune encephalomyelitis by modulating the balance between Th17 and regulatory T cells. J Immunol 187(3):1120-8 |
| abstractText | Agonistic anti-4-1BB Ab is known to ameliorate experimental autoimmune encephalomyelitis. 4-1BB triggering typically leads to the expansion of CD8(+) T cells, which produce abundant IFN-gamma, and this in turn results in IDO-dependent suppression of autoimmune responses. However, because neutralization of IFN-gamma or depletion of CD8(+) T cell only partially abrogates the effect of 4-1BB triggering, we sought to identify an additional mechanism of 4-1BB-triggered suppression of autoimmune responses using IFN-gamma- or IFN-gammaR-deficient mice. 4-1BB triggering inhibited the generation of Th17 cells that is responsible for experimental autoimmune encephalomyelitis induction and progression, and increased Foxp3(+)CD4(+) regulatory T (Treg) cells, particularly among CD4(+) T cells. This was not due to a direct effect of 4-1BB signaling on CD4(+) T cell differentiation: 4-1BB signaling not only reduced Th17 cells and increased Treg cells in wild-type mice, which could be due to IFN-gamma production by the CD8(+) T cells, but also did so in IFN-gamma-deficient mice, in that case by downregulating IL-6 production. These results show that although secondary suppressive mechanisms evoked by 4-1BB triggering are usually masked by the strong effects of IFN-gamma, 4-1BB signaling seems to modulate autoimmune responses by a number of mechanisms, and modulation of the Th17 versus Treg cell balance is one of those mechanisms. |
