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T cell dynamics during induction of tolerance and suppression of experimental allergic encephalomyelitis.

ABSTRACT: 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?R-deficient (Fc?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?R(+/+) dendritic cells (DCs) are adoptively transferred into Fc?R(-/-) mice, uptake and presentation of Ig-MOG occurs and the animals were able to overcome experimental allergic encephalomyelitis. We then fluorescently labeled Fc?R(+/+) DCs and 2D2 MOG-specific TCR-transgenic T cells, transferred them into Fc?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.

SUBMITTER: Divekar RD

PROVIDER: S-EPMC3186833 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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T cell dynamics during induction of tolerance and suppression of experimental allergic encephalomyelitis.

Divekar Rohit D RD Haymaker Cara L CL Cascio Jason A JA Guloglu Betul F BF Ellis Jason S JS Tartar Danielle M DM Hoeman Christine M CM Franklin Craig L CL Zinselmeyer Bernd H BH Lynch Jennifer N JN Miller Mark J MJ Zaghouani Habib H

Journal of immunology (Baltimore, Md. : 1950) 20110912 8

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. FcγR-deficient (FcγR(-/-)) 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 FcγR(+/+) dendritic cel ...[more]

PMID: 21911603

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Project description:Multiple sclerosis (MS) is an autoimmune disease that attacks myelinated axons in the central nervous system. Induction of oral tolerance is a potent mechanism to prevent autoimmunity. The food yeast Candida utilis was used to test the therapeutic potential of oral tolerance induction in an animal model of human multiple sclerosis (MS). We constructed a C. utilis strain, which displays a fusion peptide composed of the encephalitogenic MOG35-55 peptide and the C. utilis Gas1 cell wall protein on its surface.By immunizing mice with MOG35-55 peptide experimental autoimmune encephalomyelitis (EAE) was induced in a mouse model. Feeding of mice with C. utilis that expresses MOG35-55 peptide on its surface was started seven days prior to immunization and was continued for ten days. Control animals were treated with wild-type fungus or left untreated. Untreated mice developed first clinical symptoms ten days post immunization (p. i.) with an ascending paralysis reaching maximal clinical disability at day 18 to 20 p. i.. Treatment with the wild-type strain demonstrated comparable clinical symptoms. In contrast, oral gavage of MOG35-55-presenting fungus ameliorated the development of EAE. In addition, incidence as well as maximal clinical disease severity were significantly reduced. Interestingly, reduction of disease severity also occurred in animals treated with heat-inactivated C. utilis cells indicating that tolerance induction was independent of fungal viability. Better disease outcome correlated with reduced demyelination and cellular inflammation in the spinal cord, lower T cell proliferation against rechallenge with MOG35-55 and more regulatory T cells in the lymph nodes. Our data demonstrate successful that using the food approved fungus C. utilis presenting the immunogenic MOG35-55 peptide on its surface induced an oral tolerance against this epitope in EAE. Further studies will reveal the nature and extent of an anti-inflammatory environment established by the treatment that prevents the development of an autoimmune disorder affecting the CNS.

Dataset Information

T cell dynamics during induction of tolerance and suppression of experimental allergic encephalomyelitis.

Publications

T cell dynamics during induction of tolerance and suppression of experimental allergic encephalomyelitis.

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