Conversion of orally induced suppression of the mucosal immune response to ovalbumin into stimulation by conjugating ovalbumin to cholera toxin or its B subunit.
Oral pretreatment of mice with ovalbumin (OVA) not only suppressed a subsequently induced systemic immune response ('oral tolerance') but also suppressed, even more effectively, a subsequently induced intestinal IgA response. In contrast, pretreatment with OVA conjugated to cholera toxin (CT) or its B subunit (CTB) resulted in a stimulative effect. The stimulative effect was enhanced when unconjugated OVA and polymerized OVA were removed from the OVA-CT (B) conjugate mixtures by affinity chromatography. Thus, the effect of oral pretreatment depends on the balance between tolerizing and stimulating components in the conjugate mixture. As OVA-CTB conjugates were at least as effective as OVA-CT conjugates in stimulation of the intestinal immune response, we concluded that the ability of the OVA conjugates to bind to the intestinal mucosa is a prerequisite in inducing the stimulative effect. These observations further demonstrate that conjugation of a protein antigen to an appropriate carrier can convert the nature of the immunization from suppressive into stimulative.
Department of Immunology, Central Veterinary Institute, Lelystad, The Netherlands.
W
W
Stok
P J
PJ
van der Heijden
A T
AT
Bianchi
D000284:Administration, Oral; D000818:Animals; D002772:Cholera Toxin / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D010047:Ovalbumin / Q000276:immunology*
D007071:Immunoglobulin A, Secretory; D010047:Ovalbumin; D002772:Cholera Toxin