Oral tolerance induction by mucosal administration of cholera toxin B-coupled antigen involves T-cell proliferation in vivo and is not affected by depletion of CD25+ T cells
Article first published online: 11 MAY 2006
Volume 118, Issue 3, pages 311–320, July 2006
How to Cite
George Chandy, A., Hultkrantz, S., Raghavan, S., Czerkinsky, C., Lebens, M., Telemo, E. and Holmgren, J. (2006), Oral tolerance induction by mucosal administration of cholera toxin B-coupled antigen involves T-cell proliferation in vivo and is not affected by depletion of CD25+ T cells. Immunology, 118: 311–320. doi: 10.1111/j.1365-2567.2006.02368.x
- Issue published online: 26 MAY 2006
- Article first published online: 11 MAY 2006
- Received 16 December 2005; revised 24 February 2006; accepted 24 February 2006.
- oral tolerance;
- regulatory T cells;
- cholera toxin;
- cholera toxin B subunit
Oral administration of antigens coupled to the B subunit of the cholera toxin (CTB) can dramatically reduce the amount of antigen needed for tolerance induction and has been used in several animal models to suppress conditions where the immune system overreacts to foreign and self-antigens. In this study, the cellular events following oral administration of CTB-coupled antigen was investigated. As a model system, limited numbers of CSFE-labelled cells from influenza haemagglutinin peptide (HApep) T-cell transgenic mice were transferred to wild type mice and the mice were then given CTB-coupled HApep orally. The inductive events of CTB-induced tolerance was characterized by extensive proliferation of HApep-specific T cells in the mesenteric lymph nodes (MLNs) and in the spleen. The proliferating cells up-regulated the gut homing molecule α4β7 and down-regulated the high endothelial venule binding molecule l-selectin. Addition of the whole cholera toxin (CT) to CTB-HApep showed a similar pattern as CTB-HApep feeding, with antigen-specific proliferation in the MLN and spleen and expression of α4β7 on the proliferating cells. However, addition of CT to CTB-HApep, produced a stronger and faster proliferative response and abrogated CTB-HA mediated oral tolerance. Feeding of CTB-HApep expanded CD25+ cells in the MLNs. CTB-induced oral tolerance could, however, not be explained by CD25+ dependent regulatory activity, as oral administration of CTB-HApep to mice depleted of CD25+ cells still gave rise to systemic tolerance. Thus, several mechanisms might co-orchestrate the systemic tolerance seen in response to feeding with CTB-coupled antigen.