The B subunit of Escherichia coli heat labile enterotoxin abrogates oral tolerance, promoting predominantly Th2-type immune responses.
Mucosal antigen encounter usually results in a state of systemic non-responsiveness (tolerance). This failure to mount a protective response is a major hurdle to mucosal vaccine development. Hence, the identification of safe and effective mucosal adjuvants promoting protective immunity is of critical importance. The non-toxic B subunit of Escherichia coli heat labile enterotoxin(EtxB) is a potent nasal adjuvant; however, its usefulness following oral delivery is unconfirmed. We used DO11.10 chimeric mice to assess whether EtxB could abrogate tolerance to oral OVA. We show that admixing EtxB with OVA for oral immunization abrogates oral tolerance and results in a weak anti-OVA immune response. Importantly, EtxB profoundly modulated the nature of the response to subsequent parenteral challenge, promoting IgG1 in favor of IgG2a antibodies and depressing IFN-gamma production while elevating TGF-beta secretion. The addition of EtxB promoted T cell division, as assessed by loss of staining with carboxyfluorescein diacetate succinimidyl ester. Enhanced cell division promoted by EtxB was associated with T cell differentiation (increased numbers of CD45RBlow cells) in vivo, although dividing OVA-specific T cells were CD25-. These data suggest that although EtxB is a weak oral adjuvant, it can profoundly modulate the nature of the immune response to admixed antigen.
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol, GB.
Andrea
A
Plant
Rachel
R
Williams
Michelle E
ME
Jackson
Neil A
NA
Williams
D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002678:Chimera / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D029968:Escherichia coli Proteins; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000276:immunology*
D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C027538:heat-labile enterotoxin, E coli