Antigen-primed splenic CD8⁺ T cells impede the development of oral antigen–induced allergic diarrhea

Background

Although CD4⁺ T-cell populations are thought to be involved in the pathophysiology of food allergy and oral tolerance, the role of CD8⁺ T cells remains uncertain.

Objective

We analyzed regulatory effects of adoptively transferred CD8⁺ T cells on the development of allergic diarrhea in antigen-sensitized mice that had a significantly reduced number of conventional TCRαβ⁺ CD8⁺ T cells.

Methods

Ovalbumin-specific T-cell receptor transgenic mice were systemically sensitized to ovalbumin. Splenic CD8⁺ T cells purified from ovalbumin-sensitized or nonsensitized wild-type mice or IL-10 knockout mice were adoptively transferred to ovalbumin-sensitized ovalbumin-specific T-cell receptor transgenic mice. Allergic diarrhea induced by oral administration of ovalbumin, ovalbumin-specific immunoglobulin production, and cytokine production in intestines and mesenteric lymph nodes were assessed.

Results

Adoptive transfer of splenic CD8⁺ T cells from ovalbumin-primed mice, but not from nonprimed mice, suppressed the development of allergic diarrhea, which was associated with in vivo increased IL-10 mRNA expression and in vitro antigen-specific IL-10 production by mesenteric lymph node cells. Upregulation of serum ovalbumin-specific IgE was not suppressed by ovalbumin-primed CD8⁺ T-cell transfer. Although administration of IL-10 before ovalbumin challenge failed to alleviate allergic diarrhea, transfer of splenic CD8⁺ T cells from IL-10 knockout mice showed diminished preventive effects.

Conclusion

Systemic immunization with allergen simultaneously induces regulatory CD8⁺ T cells that can inhibit the development of allergic diarrhea. IL-10 production by regulatory CD8⁺ T cells appears to be partially involved in these inhibitory mechanisms.

Key words: Food allergy, allergic diarrhea, CD8⁺ T cells, regulatory T cells, IL-10, transgenic mice, tolerance, IgE

Abbreviations used: MLN, Mesenteric lymph node, mmcp-1, Mucosal mast cell protease 1, TCR, T-cell receptor, TCR-tg, Ovalbumin-specific T-cell receptor transgenic