Mucosal T cells induce systemic anergy for oral tolerance

Area of Science:

• Immunology
• Microbial Pathogenesis

Background:

• Heat-labile enterotoxin (LT) from enterotoxigenic Escherichia coli exhibits potent immunoregulatory properties, including inhibition of oral tolerance and adjuvanticity.
• Understanding the mechanisms of oral tolerance is crucial for developing effective oral immunization strategies.

Purpose of the Study:

• To investigate the immunoregulatory effects of an immunogenic peptide of LT, specifically LT-B(26-45), on oral tolerance induction.
• To elucidate the role of CD4+ T cells in the spleen and Peyer's patches in mediating systemic unresponsiveness.

Main Methods:

• Oral administration of LT-B(26-45) peptide to BALB/c mice.
• Assessment of serum IgG responses and T cell proliferation assays.
• RT-PCR analysis of cytokine mRNA expression (IL-2, IFN-gamma, IL-4, TGF-beta, IL-6) in spleen and Peyer's patch CD4+ T cells.
• Adoptive transfer experiments using LT-B-specific intraepithelial lymphocytes.

Main Results:

• Oral administration of LT-B(26-45) induced systemic unresponsiveness, characterized by diminished serum IgG responses.
• Spleen CD4+ T cells from tolerized mice failed to proliferate and lacked IL-2 mRNA, indicating T cell anergy.
• Peyer's patch CD4+ T cells from tolerized mice produced IFN-gamma, IL-2, IL-4, and TGF-beta mRNA.
• Adoptive transfer of specific lymphocytes abrogated the induced tolerance.
• LT-B(26-45)-stimulated spleen CD4+ T cells in reversed tolerance expressed IFN-gamma, IL-2, IL-4, and IL-6 mRNA.

Conclusions:

• Peyer's patch CD4+ T cells play a critical role in inducing oral tolerance.
• Systemic T cell anergy, driven by events in the Peyer's patches, is the mechanism underlying LT-induced oral tolerance.