T Cell Dynamics during Induction of Tolerance and Suppression of Experimental Allergic Encephalomyelitis

The cell dynamics associated with induction of peripheral T cell tolerance remain largely undefined. In this study, an in vivo model was adapted to two-photon microscopy imaging, and T cell behavior was analyzed on tolerogen-induced modulation. Fc gamma R-deficient (Fc gamma R(-/-)) mice were unable to resist or alleviate experimental allergic encephalomyelitis when treated with Ig-myelin oligodendrocyte glycoprotein (MOG) tolerogen, an Ig carrying the MOG35-55 peptide. However, when Fc gamma R(+/+) dendritic cells (DCs) are adoptively transferred into Fc gamma R(-/-) mice, uptake and presentation of Ig-MOG occurs and the animals were able to overcome experimental allergic encephalomyelitis. We then fluorescently labeled Fc gamma R(+/+) DCs and 2D2 MOG-specific TCR-transgenic T cells, transferred them into Fc gamma R(-/-) mice, administered Ig-MOG, and analyzed both T cell-DC contact events and T cell motility. The results indicate that tolerance takes place in lymphoid organs, and surprisingly, the T cells do not become anergic but instead have a Th2 phenotype. The tolerant Th2 cells displayed reduced motility after tolerogen exposure similar to Th1 cells after immunization. However, the Th2 cells had higher migration speeds and took longer to exhibit changes in motility. Therefore, both Th1 immunity and Th2 tolerance alter T cell migration on Ag recognition, but the kinetics of this effect differ among the subsets. The Journal of Immunology, 2011, 187: 3979-3986.