Adjuvant Costimulation during Secondary Antigen Challenge Directs Qualitative Aspects of Oral Tolerance Induction, Particularly during the Neonatal Period

Abstract

In this report we demonstrate that although passive feeding of specific Ag to mice as neonates or adults can induce oral tolerance in both the cellular and humoral arms of the immune response, quantitative and, in particular, qualitative aspects of the tolerance process are determined by the nature of the inflammatory costimuli provided at the time of secondary Ag challenge. Moreover, this dependency upon nonspecific costimulation is more profound in Ag-fed neonates than in their adult counterparts. Thus, administration of Ag in the Th1-selective adjuvant CFA to prefed animals resulted in significant inhibition of IgG2a, IL-2, and IFN-γ responses, whereas IL-5 responses were increased. In contrast, rechallenge with Ag in the Th2-selective adjuvant aluminum hydroxide resulted in significant inhibition of IgG1, IgE, IL-2, and IL-5 responses, whereas IFN-γ responses were increased. Additionally, although soluble Ag challenge of prefed adults revealed marginal tolerogenic effects, the same challenge protocol in animals prefed as neonates elicited enhanced Th2-dependent IgG1 production. These results suggest that inflammatory stimulation at the time of Ag challenge is obligatory to trigger oral tolerance mechanisms, particularly in animals fed as neonates and also that the type of adjuvant used at the time of challenge selects for the type of Th cell population to be inhibited.

Convergence of Itch-induced ubiquitination with MEKK1-JNK signaling in Th2 tolerance and airway inflammation

“…To better understand the biological role of Itch in T cell tolerance, we established an in vivo mouse model of immune tolerance. In this model, mice were immunized s.c. with an OVA-derived antigenic peptide conjugated with either CFA to induce a Th1 response, or alum to elicit a Th2 reaction (23). In addition, the mice received concurrent i.p.…”

In Vitro and In Vivo Down-Regulation of Regulatory T Cell Activity with a Peptide Inhibitor of TGF-β1

“…Bacteria were diluted 200-fold in GM17E medium, incubated at 30°C overnight, harvested by centrifugation, and concentrated in BM9 medium at 2 ϫ 10 9 bacteria/100 l. Treated mice, received 100 l of this suspension daily by intragastric catheter (46). DO11.10 mice were sensitized by s.c. injection of 100 g of OVA in 50 l of a 1:1 CFA (Difco) saline solution in the tail base at day 1 (47). Mice were fed BM9 as a control or LL-OVA (both at days 1-5 and days 8 -12) administrations using a stainless 18-gauge animal feeding needle.…”

Density of dendritic cells in the human tracheal mucosa is age dependent and site specific

“…18 19 A recent study suggested that adjuvant co-stimulation triggers oral tolerance mechanisms in neonatal mice. 20 The development of neonatal immunity in respect to allergic diseases in childhood and in adults is of clinical relevance. DC are necessary for the initiation and modulation of T cell responses and are involved in immunoregulation early in life.…”