Beta 2-microglobulin-dependent NK1.1+ T cells are not essential for T helper cell 2 immune responses.
A number of investigations have established the critical role of interleukin 4 (IL-4) in mediating the development of T helper (Th)2 effector cells in vitro and in vivo. Despite intensive study, the origin of the 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 priming. These cells are selected by the nonpolymorphic major histocompatibility complex (MHC) class I molecule, CD1, and are deficient in beta 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 mount Th2 immune responses after challenge with a number of well-characterized antigens administered by a variety of routes. As assessed by immunization with protein antigen, infection with Leishmania major, embolization with eggs of Schistosoma mansoni, intestinal infection with Nippostrongylus brasiliensis, or induction of airway hyperreactivity to aerosolized antigen, beta 2m-deficient mice developed functional type 2 immune responses that were not substantially different than those in wild-type mice. Production of IL-4 and the generation of immunoglobulin 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 indicate that beta 2m-dependent NT cells are not required for Th2 development in vivo.
Brown
D R
DR
Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Illinois 60637, USA.
Fowell
D J
DJ
Corry
D B
DB
Wynn
T A
TA
Moskowitz
N H
NH
Cheever
A W
AW
Locksley
R M
RM
Reiner
S L
SL
D000818:Animals; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D005069:Evaluation Studies as Topic; D005260:Female; D006099:Granuloma / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D007109:Immunity; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008174:Lung Diseases, Parasitic / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D012555:Schistosomiasis mansoni / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency*
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D001613:beta 2-Microglobulin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin