Th2 Subset
Furthermore, in mouse studies it was found that a probiotic mixture of nine different bacterial strains ameliorated recurrent Th1-mediated murine colitis by inducing IL-10 secretion and promoting development of IL-10 dependent TGF-β bearing regulatory cells. Daily administration of 2 mg (approximately 3 billion bacteria) of this probiotic mixture for three weeks to mice during a remission period induced an immunoregulatory response involving TGF-β secreting cells and, therefore, resulted in a milder form of recurrent colitis. These two studies support the therapeutic use of certain strains of probiotics in different animal species to prevent and moderate diseases associated with chronic Th1 cell dominance.
Th2 Subset
The Th2 cell pathway supports humoral immunity by activating specific B cells and promoting antibody class switching. Th2 cells release the cytokines IL-4, IL-13, IL-5 and IL-10 that activate antibody formation or release from immune cells like B cells, mast cells or eosinophils7. Persistent, uncontrolled Th2 activation is associated with diseases like atopy (including allergies, eczema, asthma, and allergic rhinitis), chronic fatigue and immunodeficiency syndrome, eosinophilic rhinosinusitis, ulcerative colitis and possibly certain cancers.
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Many studies in the past decade have shown that specific probiotic strains can benefit allergic diseases characterized by this chronic expression of Th2 cell-related cytokines. For example, Pochard et al. (2002) in an in vitro study demonstrated that different Lactobacillus strains reduce IL-4 levels (a Th2 cytokine) and enhance production of Th2 cell-related cytokines, supporting a more balanced Th1/ Th2 response.11 More specifically, a three-hour incubation of L. plantarum, L. lactis, L. casei and L. rhamnosus GG (at a concentration of ten bacteria per purified CD4+T cell) inhibited the production of IL-4 and IL-5 in a dose-dependent manner from human polymorphonuclear cells and stimulated the production of the pro Th1 cell cytokines, IFN-γ and IL- 12. In the same experiment, no significant inhibition of IL-4 and IL-5 secretion occurred when the cells were incubated with Escherichia coli TG1, demonstrating that the inhibition of cytokine secretion was specific to certain bacterial strains. It was postulated that supplementation with these specific Lactobacillus strains could benefit patients with allergic diseases by reducing Th2 cytokine production.
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Other studies have shown that L. rhamnosus GG can reduce allergic disease symptoms in humans. Ingestion of therapeutic levels of L. rhamnosus GG by breast-feeding mothers and newborn babies resulted in a 50% inhibition of the risk of developing atopic eczema in babies.12,13 These studies provide an example of how administration of strainspecific probiotics can modulate the immune response and down-regulate the Th2 dominance associated with the development of allergies.
Regulatory T cells
There are other subsets of T cells, termed type 1 T regulatory cells (Treg) or Type 3 T regulatory cells (Th3) that help regulate T-helper cell functions and maintain intestinal homeostasis. For example, Treg cells predominantly secret IL-10, a cytokine that down-regulates Th1 activity and, therefore, reduces Th1-associated inflammation. Adequately primed Th3 cells primarily secrete TGF-β, which helps modulate both Th1 and Th2 activity7 (see figure 1). There is increased understanding that Treg and Th3 cells are influential in the maintenance of mucosal immunity and, therefore, the prevention of pathology. Furthermore, certain probiotic strains can moderate these regulatory responses. For example, L. paracasei (NCC2461) stimulates in vitro regulatory T cells to produce TGF-beta and IL-10, cytokines implicated in the oral tolerance response to bovine betalactoglobulin in mice. Artificial induction of the oral tolerance response, via the administration of strain-specific probiotics, would help modulate hypersensitivity reactions.