Given their regulatory effects, it is not surprising that 'old friends' can be shown to drive immunoregulation, and to block or treat pathophysiology in models of allergies, autoimmune disease and IBD 29, 38, 39.
Vaccines using genetically modified LAB as mucosal antigen delivery vehicles have been tested in mouse models of allergies to house dust mites [ 27– 29], eggs [ 30], birch pollen [ 31], Japanese cedar pollen [ 32], and cow's milk [ 33].
Elevated IL-9 production and Th9 differentiation have been demonstrated in mouse models of allergy and melanoma [ 54, 55].
Prior to clinical development of the T cell epitope peptide therapies, murine models of allergy were developed to validate the strategy and further explore mechanisms.
Passive cutaneous anaphylaxis (PCA) is the gold standard method to measure allergen-specific IgE antibody levels in mouse models of allergy.
Impairment of immune tolerance has been shown to augment disease in various models of allergy and/or autoimmunity, including diabetes onset in NOD mice [ 18, 19], collagen-induced arthritis [ 20, 21], and experimental colitis [ 22].
Many studies reporting successful peptide immunotherapy in murine models of allergy demonstrated that administration of immunodominant T cell epitope peptides of major allergens induced tolerance not only to those peptides but also to purified allergen and whole allergen extracts 30– 30.
Different strains of bifidobacteria were shown to have profound effects on dendritic cells, macrophage, and T cells of healthy humans and in animals models of allergy or intestinal inflammation [ 42– 42].
The effects of LPS on Th2 responses in animal models of allergy remain uncertain as LPS has been demonstrated to increase (Delayre-Orthez et al., 2004), decrease (Gerhold et al., 2002; Rodríguez et al., 2003; Komlósi et al., 2006) and not alter (Murakami et al., 2007) them.
Subsequently, similar findings confirming the robustness of anergy, linked suppression and changes in cytokine functional phenotype induced by dominant T cell epitope peptides were reported for murine models of allergy to birch pollen [ 83], Japanese cedar pollen [ 84, 85], olive pollen [ 86], bee and hornet venom [ 87], bee venom [ 88], cat [ 89], egg-white [ 90] and Timothy grass pollen [ 91].
LPS contamination in allergen preparations has been raised as an issue in many models of allergy, however we believe that approaching these studies using household components with naturally occurring LPS more closely and accurately reflects the environment in which one develops asthma.
