BETA-2-MICROGLOBULIN-DEPENDENT NK1.1(-CELLS ARE NOT ESSENTIAL FOR T-HELPER CELL 2 IMMUNE-RESPONSES() T)

A number of investigations have established the critical role of inter leukin 4 (IL-4) in mediating the development of T helper (Th)2 effecto r cells in vitro and in vivo. Despite intensive study, the origin of t he IL-4 required for Th2. priming and differentiation remains unclear. Natural killer (NK)1.1(+) alpha/beta T cell receptor(+) T (NT) cells, a unique lineage of cells capable of producing large amounts of IL-4 after activation in vivo, are important candidates for directing Th2 p riming. These cells are selected by the nonpolymorphic major histocomp atibility complex (MHC) class I molecule, CD1, and are deficient in be ta 2-microglobulin (beta 2m)-null mice. We used beta 2m-deficient mice on both BALB/c and C57BL/6 backgrounds to examine their capacity to m ount Th2 immune responses after challenge with a number of well-charac terized antigens administered by a variety of routes. As assessed by i mmunization with protein antigen, infection with Leishmania major, emb olization with eggs of Schistosoma mansoni, intestinal infection with Nippostrongylus brasiliensis, or induction of airway hyperreactivity t o aerosolized antigen, beta 2m-deficient mice developed functional typ e 2 immune responses that were not substantially different than those in wild-type mice. Production of IL-4 and the generation of immunoglob ulin E (IgE) and eosinophil responses were preserved as assessed by a variety of assays. Collectively, these results present a comprehensive analysis of type 2 immune responses in beta 2m-deficient mice, and in dicate that beta 2m-dependent NT cells are not required for Th2 develo pment in vivo.