Abstract
Monoclonal antibodies (mAb) have been shown effective in inducing immune tolerance in a range of animal models of autoimmunity, allergy, and transplantation. We investigated whether CD4-blockade, effective in inducing transplantation tolerance, could prevent systemic immune responses leading to anaphylaxis. We found that treatment with a non-depleting anti-CD4 mAb could prevent peanut-induced anaphylaxis following subsequent systemic exposure to crude peanut extract (CPE). Furthermore, the effect of CD4-blockade did not interfere with overall immune competence, as anti-CD4 treated mice remained fully competent to respond to unrelated antigens. Protection from anaphylaxis correlated with increased frequency of Foxp3+ regulatory T cells (Treg), and was abrogated following Treg depletion. Taken together our data suggest that activation of T cells by CPE in presence of CD4-blockade leads to Treg expansion that can prevent peanut-induced anaphylaxis.
Highlights
Anaphylaxis is an acute, life-threatening, allergic reaction where a physiologic process that normally acts in a local and limited manner to protect against infection occurs massively and systemically
Experiments with TCR-transgenic mice have shown the tolerant state is maintained by Foxp3+ Treg cells that can be induced from Foxp3− precursors (Cobbold et al, 2004; Oliveira et al, 2011)
We cannot exclude that part of the effect of CD4-blockade is due to activation-induced cell death of T cells specific for the antigen present at the time of tolerance induction – a mechanism well described in transplantation tolerance induced with co-stimulation blockade (Li et al, 1999b; Wells et al, 1999)
Summary
Anaphylaxis is an acute, life-threatening, allergic reaction where a physiologic process that normally acts in a local and limited manner to protect against infection occurs massively and systemically. Monoclonal antibodies (mAb) that target T cell co-receptor and co-stimulatory molecules have been reported effective in inducing tolerance to non-self antigens. It was reported that a non-depleting anti-CD4 mAb was effective in preventing allergic airways disease in mice sensitized with ovalbumin (OVA; Li et al, 1999a). We have recently extended these data, showing that tolerance can be induced in mice to a clinically relevant aeroallergen – house dust mite (HDM). In this case, tolerant mice were protected from airways hyperreactivity (AHR), eosinophilia, goblet cell hyperplasia, and production of antigen-specific IgG1 and Abbreviations: AHR, airway hyperreactivity; Alum, aluminum hydroxide; CPE, crude peanut extract; HDM, house dust mite; i.p., intra peritoneal; mAb, monoclonal antibody; OVA, ovalbumin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
