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 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 antigenically naive alpha/beta+ T cells into Th2 cells. Murine NK1.1+ (CD4+ or CD4-CD8-) alpha/beta+ T cells comprise a beta 2-microglobulin (beta 2m)-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. alpha/beta+ CD8+ T cells, most of which require beta 2m for their development, have also been proposed as positive regulators of allergen-induced Th2 responses. We tested whether beta 2m-dependent T cells were essential for Th2 cell-mediated allergic reactions by treating wild-type, beta 2m-deficient (beta 2m -/-), 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 beta 2m -/- 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 node 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+ alpha/beta+ T cell population, as well as other beta 2m-dependent populations, such as most peripheral alpha/beta+ CD8+ T cells, are dispensable for the Th2 pulmonary response to protein allergens.
Zhang
Y
Y
Department of Pediatrics, University of Washington, Seattle 98195, USA.
Rogers
K H
KH
Lewis
D B
DB
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000032:analysis; D000950:Antigens, Ly; D000954:Antigens, Surface; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D007073:Immunoglobulin E / Q000032:analysis; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000172:deficiency / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D037181:Lectins, C-Type; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010047:Ovalbumin / Q000276:immunology; D011506:Proteins / Q000032:analysis; D011657:Pulmonary Eosinophilia; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000378:metabolism*
D000485:Allergens; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D018793:Interleukin-13; D015848:Interleukin-5; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D001613:beta 2-Microglobulin; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin