Autoantigen Immunization at Different Sites Reveals a Role for Anti-Inflammatory Effects of IFN-γ in Regulating Susceptibility to Experimental Autoimmune Encephalomyelitis
- 1 May 2009
- journal article
- research article
- Published by The American Association of Immunologists
- Vol. 182 (9), 5268-5275
- https://doi.org/10.4049/jimmunol.0800681
Abstract
Experimental autoimmune encephalomyelitis is induced in B10.PL (H-2u) mice by immunization with the immunodominant N-terminal epitope of myelin basic protein, Ac1-9. In the present study, we show that the site of immunization impacts disease incidence and severity. This effect is more marked in female mice than in males. Although immunization in the flanks is effective in eliciting disease, delivery of Ag in the footpad and tailbase results in poor induction. Analyses of the immune responses in female mice following different immunization regimens indicates that resistance to disease is accompanied by higher levels of IFN-γ and CD11b+Gr-1int myeloid cells. Such myeloid cells are known to have a suppressive function, and consistent with this knowledge, blockade of IFN-γ results in increased disease activity and decreased levels of splenic CD11b+Gr-1int cells. Conversely, injection of adjuvants (CFA or Pam3CSK4) in the footpad decreases experimental autoimmune encephalomyelitis incidence and severity. Our study indicates that the site of immunization can impact the magnitude of the ensuing inflammatory response, and that at a certain threshold a protective, regulatory circuit can be elicited.Keywords
This publication has 48 references indexed in Scilit:
- Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammationNature Medicine, 2007
- A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17Nature Immunology, 2005
- Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineagesNature Immunology, 2005
- IL-23 drives a pathogenic T cell population that induces autoimmune inflammationThe Journal of Experimental Medicine, 2005
- Flow cytometric quantification of apoptosis and proliferation in mixed lymphocyte cultureCytometry Part A, 2003
- Multiple Sclerosis: Deeper Understanding of Its Pathogenesis Reveals New Targets for TherapyAnnual Review of Neuroscience, 2002
- Failure to Suppress the Expansion of the Activated Cd4 T Cell Population in Interferon γ–Deficient Mice Leads to Exacerbation of Experimental Autoimmune EncephalomyelitisThe Journal of Experimental Medicine, 2000
- T Cell Deletion in High Antigen Dose Therapy of Autoimmune EncephalomyelitisScience, 1994
- Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunityCell, 1993
- Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapyCell, 1988