Western countries are being confronted with a disturbing increase in the incidence of most immune disorders, including autoimmune and allergic diseases. Converging epidemiological evidence indicates that this increase is linked to improvement of the socio-economic level of these countries. Epidemiological and clinical data support the hygiene hypothesis according to which the decrease of infections observed over the last three decades is the main cause of the incessant increase in immune disorders.
Independently of the need for confirmation by epidemiological prospective studies, the hygiene hypothesis still poses numerous questions concerning the nature of protective infectious agents, the timing of their involvement with regard to the natural history of immune diseases and, most importantly, the mechanisms of protection.
Three orders of mechanisms are being explored. Antigenic competition is the first hypothesis (immune responses against pathogens compete with autoimmune and allergic responses). Its discussion in the context of homeostatic regulation of lymphocyte pools has shed new light on this hypothesis. Infectious agents may also intervene through components, which are not recognized as antigens but bind to specific receptors on cells of the immune system. Major attention has recently been drawn to Toll receptors and TIM proteins present on Th cells, which may express the function of the virus receptor. Another hypothesis deals with immunoregulation. Infectious agents stimulate a large variety of regulatory T cells (Th2, CD25+, Tr1, NKT,…) whose effects extend to other specificities than those which triggered their differentiation (bystander suppression).