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Oral tolerance in EAE: reversal of tolerance by T helper cell cytokines
1Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock 72205, USA. kkelly@biomed.uams.edu
Abstract:
Oral administration of myelin basic protein (MBP) inhibits clinical and histopathological manifestations of experimental autoimmune encephalomyelitis (EAE), but only partially reduces serum anti-MBP antibody titers. We report here that orally administered MBP alters the isotypic distribution of anti-MBP antibody-forming cells (AFC) among various lymphoid tissues, with the most profound differences seen in mucosal tissues. We observed an isotype-selective reduction in anti-MBP IgA but not IgM AFC frequencies in Peyer's patches. The anti-MBP IgA AFC frequencies could be reconstituted by addition of interleukin 4 (IL-4) and interleukin 5(IL-5). The cytokines did not appear to generate de novo responses since no increases in anti-MBP lgA AFC frequencies were observed in control cultures. These results indicate that decreased antibody production, as a result of oral antigen administration, can be reversed by exposure to the appropriate cytokines.
Insights
Oral administration of myelin basic protein (MBP) impacts immune responses in experimental autoimmune encephalomyelitis (EAE). Cytokines like IL-4 and IL-5 can restore reduced IgA antibody production in Peyer's patches.
Area of Science:
- Immunology
- Neuroscience
- Oral Tolerance
Background:
- Oral administration of myelin basic protein (MBP) partially reduces experimental autoimmune encephalomyelitis (EAE) symptoms and serum antibody titers.
- The effect of oral MBP on the distribution and isotype of antibody-forming cells (AFC) in lymphoid tissues is not fully understood.
Purpose of the Study:
- To investigate how orally administered MBP influences the isotypic distribution of anti-MBP AFC in various lymphoid tissues.
- To determine the role of cytokines, specifically IL-4 and IL-5, in reconstituting anti-MBP IgA AFC frequencies.
Main Methods:
- Mice were orally administered MBP.
- Anti-MBP antibody-forming cells (AFC) were analyzed for isotype distribution in different lymphoid tissues, including Peyer's patches.
- In vitro cultures were used to assess the effect of IL-4 and IL-5 on anti-MBP IgA AFC frequencies.
Main Results:
- Oral MBP administration altered the isotypic distribution of anti-MBP AFC, particularly in mucosal tissues.
- A significant reduction in anti-MBP IgA AFC frequencies was observed in Peyer's patches, while IgM AFC frequencies remained unaffected.
- Addition of IL-4 and IL-5 reconstituted the anti-MBP IgA AFC frequencies in Peyer's patches without inducing de novo responses.
Conclusions:
- Oral antigen administration can lead to isotype-selective decreases in antibody production.
- The observed decrease in anti-MBP IgA AFC frequencies can be reversed by appropriate cytokine exposure (IL-4 and IL-5).
- This suggests a mechanism for modulating mucosal immune responses through cytokine intervention.