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The hyperresponsiveness of W/W(v) mice to oral sensitization is associated with a decrease in TCRgammadelta-T cells.
Haruyo Okunuki1, Reiko Teshima, Yuji Sato
1Division of Biochemistry and Immunochemistry, National Institute of Health Sciences, Japan.
Biological & Pharmaceutical Bulletin
|April 2, 2005
Summary
Gamma delta T cells (gammadelta-IELs) play a crucial role in oral tolerance. Reduced gammadelta-IELs enhance oral sensitization, while increased numbers promote tolerance to food antigens.
Area of Science:
- Immunology
- Gastroenterology
Background:
- WBB6F1-W/W(v) mice with c-kit mutations exhibit heightened oral sensitization susceptibility.
- These mice also show a reduced proportion of intraepithelial lymphocytes expressing T cell receptor gamma delta (gammadelta-IELs).
Purpose of the Study:
- To investigate the inhibitory role of gammadelta-IELs in oral sensitization.
- To elucidate the relationship between gammadelta-IELs and oral tolerance to food antigens.
Main Methods:
- Wild-type mice treated with anti-TCRgammadelta antibody were orally sensitized with ovalbumin (OVA).
- Bone marrow-reconstituted W/W(v) mice were orally sensitized with OVA.
- OVA-specific IgG1 antibody production, active systemic anaphylaxis (ASA), and cytokine profiles were analyzed.
Main Results:
- Anti-TCRgammadelta antibody treatment in wild-type mice led to enhanced OVA-specific IgG1 production, ASA, and Th2-dominant cytokine responses.
- Bone marrow-reconstituted W/W(v) mice, with restored gammadelta-IEL levels, showed no significant enhancement in OVA-specific IgG1 or ASA.
- Reconstituted mice exhibited higher gammadelta-IEL proportions compared to untreated W/W(v) mice.
Conclusions:
- A decrease in gammadelta-IELs enhances oral sensitization.
- An increase in gammadelta-IELs diminishes oral sensitization, suggesting a role in oral tolerance.
- gammadelta-IELs are critical for establishing oral tolerance to food antigens.