The clinical experience just reviewed outlines the difficulties of treating patients with established T1D. The preventive effect of infections on the progression of β cell aggression, which represents the basis of the hygiene hypothesis, applies to the early phases of the natural history of the disease . It is thus logical to postulate that intervention aimed at ‘reprogramming’ the β cell-specific autoimmune response, as did infections in
the past, might represent a simple and robust way to prevent T1D, inasmuch as the treatment proposed is totally safe (because by definition it will concern Cobimetinib molecular weight very young and still ‘healthy’ subjects). The search for such treatments is strictly dependent upon a better understanding of the immune mechanisms underlying the hygiene hypothesis. Subsets of helper CD4+ T lymphocytes could be identified https://www.selleckchem.com/products/epacadostat-incb024360.html on the basis of the array of cytokines they produced. T helper type 1 (Th1) CD4+ T cells produce preferentially interleukin (IL)-2 and interferon (IFN)-γ that essentially support T cell growth, macrophage activation and cell-mediated immunity. Th2 cells produce IL-4, IL-6, IL-10 and IL-13, which contribute to antibody production. More recently described Th17 cells are a major source of IL-17 and IL-21.
The development of most autoimmune diseases involves cell co-operation processes with Th1 and Th17 CD4+ cells, whereas the development of allergic diseases requires IL-4 and IL-5 produced by Th2 cells. Based on initial reports pointing to the reciprocal down-regulation of Th1 and Th2 cells, Florfenicol some authors have suggested that in developed countries the lack of microbial burden in early childhood, which normally favours strong Th1-biased immunity, redirects the immune response towards a Th2 phenotype
and therefore predisposes the host to allergic disorders. The problem with such an explanation was, however, that Th1 responses in the case of autoimmunity are not protective but pathogenic. These observations would fit with the concept of a common mechanism underlying infection-mediated protection against autoimmunity and allergy. Specialized subsets of T lymphocytes defined generally as regulatory T cells will be suitable candidates, as there is compelling data to show that they are highly effective in controlling both Th1- and Th2-mediated responses. A second mechanism with relevance to the influence of infection on allergy and autoimmunity is antigenic competition, in which the immune response to an antigen is decreased by a concomitant immune response against an unrelated antigen. The competition is maximal when the unrelated antigen is administered a few days after the administration of the first antigen.