Transient blockade of CD40 ligand dissociates pathogenic from protective mucosal immunity
Arno Hänninen, … , William R. Heath, Leonard C. Harrison
Arno Hänninen, … , William R. Heath, Leonard C. Harrison
Published January 15, 2002
Citation Information: J Clin Invest. 2002;109(2):261-267. https://doi.org/10.1172/JCI13720.
View: Text | PDF
Article

Transient blockade of CD40 ligand dissociates pathogenic from protective mucosal immunity

Abstract

Antigen administration via oral and other mucosal routes can suppress systemic immunity to the antigen and has been used to prevent experimental autoimmune disease. This approach may prove ineffective or even harmful if it leads to a concomitant induction of cytotoxic T lymphocytes (CTLs), and indeed, mucosal administration of the model antigen ovalbumin (OVA) has been shown to elicit CTL activation while simultaneously inducing oral tolerance. Here we show that induction by oral OVA of CTLs in wild-type mice, and of diabetes in mice expressing OVA transgenically in pancreatic β cells, can be prevented by transiently blocking the CD40 ligand (CD40L). However, CD40L blockade did not diminish oral tolerance, as measured by suppression of systemic OVA-primed T cell proliferation, IFN-γ secretion, and Ab production. Consistent with these findings, mice lacking CD40 expression could be orally tolerized to OVA. Transient CD40L blockade therefore dissociates pathogenic from protective immunity and should enhance the efficacy and safety of oral tolerance for preventing autoimmune disease.

Authors

Arno Hänninen, Nathan R. Martinez, Gayle M. Davey, William R. Heath, Leonard C. Harrison

×

Figure 6

Options: View larger image (or click on image) Download as PowerPoint
Oral tolerance can be induced in CD40-deficient mice. B6 mice were irrad...
Oral tolerance can be induced in CD40-deficient mice. B6 mice were irradiated and reconstituted with bone marrow from either wild-type B6 or CD40 knockout mice. Mice were fed PBS or 20 mg OVA in PBS on three alternating days. As described in the legend to Figure 5, mice (n = 3 in each group) were then immunized subcutaneously with OVA in CFA. Ten days later, their spleens were harvested for measurement of T cell proliferation (not shown, see text) and IFN-γ ELIspots in the absence or presence (black bars) of 0.1 mg/ml OVA (mean and SD are shown). No ELIspots were detected in the absence of OVA.