Cytokine production by allergen-specific T cells is crucial in establishing and maintaining the tolerant or inflammatory context of allergen recognition, Production of Th2 cytokines is associated with allergic diseases including asthma. The nonallergic phenotype has historically been associated either with a failure to recognize the allergen (immunologic ignorance) or the expression of a “protective” Th1 cytokine profile. Indeed, Th1 cytokine profiles have been reported in nonallergic individuals in response to allergen. However, Th1 responses to allergens would be expected to give rise to inflammatory responses such as delayed-type hypersensitivity reactions, which is not generally the case. Thus, allergic individuals respond to allergen with an inflammatory Th2 response, whereas nonallergic individuals appear to make an immune response that is associated with Th1 cytokines but is noninflammatory.
Studies suggest that active regulation is an essential element in maintaining noninflammatory peripheral tolerance to allergens in healthy individuals. Blood T cells were stimulated with aeroallergens and/or food allergens and subsequently selected on the basis of allergen-induced cytokine production. The profile of allergen-specific interferon (IFN)-^ (Th1 marker), IL-4 (Th2 marker), and IL-10 (antiinflammatory cytokine and marker [Tr1] of a population of regulatory T cells [Treg]) production differed between allergic and nonallergic subjects, with the ratio of cell numbers secreting these three cytokines determining the development of a healthy or allergic immune response. Thus, lowTr1 numbers and high Th2 cell numbers resulted in an allergic response, whereas in nonallergic individuals a mixed Th1/Th2 response was associated with a strong IL-10 response.14 Similarly, T-cell clones derived from children persistently allergic to cow milk produced Th2 cytokines (IL-4, IL-13), whereas allergic control subjects without cow milk allergy (but allergic to another food) produced a mixed Th1/Th2 response associated with markedly elevated IL-10 levels. Continue reading “Regulatory T Cells in Allergy and Asthma: Allergen-Specific Responses in Nonallergic Individuals”