β2-Microglobulin-dependent T cells are dispensable for allergen- induced T helper 2 responses

Abstract

CD4+ and CD8+ α/β+ T cells of the T helper cell (Th)2 phenotype produce the cytokines IL-4, IL-5, and IL-13 that promote IgE production and eosinophilic inflammation. IL-4 may play an important role in mediating the differentiation of antigenetically naive α/β+ T cells into Th2 cells. Murine NK1.1+ (CD4+ or CD4 CD8+) α/β T cells comprise a β2- microglobulin (β2m)-dependent cell population that rapidly produces IL-4 after cell activation in vitro and in vivo and has been proposed as a source of IL-4 for Th2 cell differentiation, α/β+ CD8+ T cells, most of which require β2m for their development, have also been proposed as positive regulators of allergen-induced Th2 responses. We tested whether β2m- dependent T cells were essential for Th2 cell-mediated allergic reactions by treating wild-type, β2m-deficient (β2m-/-_, and IL-4-deficient (IL-4-/-) mice of the C57BL/6 genetic background with ovalbumin (OVA), using a protocol that induces robust allergic pulmonary disease in wild-type mice. OVA- treated β2m-/- mice had circulating levels of total and OVA-specific IgE, pulmonary eosinophilia, and expression of IL-4, IL-5, and IL-13 mRNA in bronchial lymph ode tissue similar to that of OVA-treated wild-type mice. In contrast, these responses in OVA-treated IL-4-/- mice were all either undetectable or markedly reduced compared with wild-type mice, confirming that IL-4 was required in this allergic model. These results indicate that the NK1.1+ α/β+ T cells population, as well as other β2m-dependent populations, such as most peripheral α/β+ CD8+ T cells, are dispensable for the Th2 pulmonary response to protein allergens.