BETA-2-MICROGLOBULIN-DEPENDENT T-CELLS ARE DISPENSABLE FOR ALLERGEN-INDUCED T-HELPER-2 RESPONSES

CD4(+) and CD8(+) alpha/beta(+) T cells of the T helper cell (Th)2 phe notype produce the cytokines IL-4, IL-5, and IL-13 that promote IgE pr oduction and eosinophilic inflammation. IL-4 may play an important rol e in mediating the differentiation of antigenically naive alpha/beta() T cells into Th2 cells. Murine NK1.1(+) (CD4(+) or CD4(-)CD8(-)) alp ha/beta(+) T cells comprise a beta 2-microglobulin (beta 2m)-dependent cell population that rapidly produces IL-4 after cell activation in v itro and in vivo and has been proposed as a source of IL-4 for Th2 cel l differentiation. alpha/beta(+) CD8(+) T cells, most of which require beta 2m for their development, have also been proposed as positive re gulators of allergen-induced Th2 responses. We tested whether beta 2m- dependent T cells were essential for Th2 cell-mediated allergic reacti ons by treating wild-type, beta 2m-deficient (beta 2m -/-), and IL-4-d eficient (IL-4 -/-) mice of the C57BL/6 genetic background with ovalbu min (OVA), using a protocol that induces robust allergic pulmonary dis ease in wild-type mice. OVA-treated beta 2m -/- mice had circulating l evels of total and OVA-specific IgE, pulmonary eosinophilia, and expre ssion of IL-4, IL-5, and IL-13 mRNA in bronchial lymph node tissue sim ilar to that of OVA-treated wild-type mice. In contrast, these respons es in OVA-treated IL-4 -/- mice were all either undetectable or marked ly reduced compared with wild-type mice, confirming that IL-4 was requ ired in this allergic model. These results indicate that the NK1.1(+) alpha/beta(+) T cell population, as well as other beta 2m-dependent po pulations, such as most peripheral alpha/beta(+) CD8(+) T cells, are d ispensable for the Th2 pulmonary response to protein allergens.