title: CD44 is critical for airway accumulation of antigen-specific Th2, but not Th1, cells induced by antigen challenge in mice.
abstract: CD44 is a cell adhesion molecule involved in lymphocyte infiltration of inflamed tissues. We previously demonstrated that CD44 plays an important role in the development of airway inflammation in a murine model of allergic asthma. In this study, we investigated the role of CD44 expressed on CD4(+)  T cells in the accumulation of T-helper type 2 (Th2) cells in the airway using CD44-deficient mice and anti-CD44 monoclonal antibodies. Antigen-induced Th2-mediated airway inflammation and airway hyperresponsiveness (AHR) in sensitized mice were reduced by CD44-deficiency. These asthmatic responses induced by the transfer of antigen-sensitized splenic CD4(+)  T cells from CD44-deficient mice were weaker than those from WT mice. Lack of CD44 failed to induce AHR by antigen challenge. Expression level and hyaluronic acid receptor activity of CD44, as well as Neu1 sialidase expression on antigen-specific Th2 cells, were higher than those on antigen-specific Th1 cells. Anti-CD44 antibody preferentially suppressed the accumulation of those Th2 cells in the airway induced by antigen challenge. Our findings indicate that CD44 expressed on CD4(+)  T cells plays a critical role in the accumulation of antigen-specific Th2 cells, but not Th1 cells, in the airway and in the development of AHR induced by antigen challenge.
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan. kshigeki@med.kawasaki-m.ac.jp
authors.forename: Shigeki
authors.initials: S
authors.lastname: Katoh
authors.forename: Osamu
authors.initials: O
authors.lastname: Kaminuma
authors.forename: Takachika
authors.initials: T
authors.lastname: Hiroi
authors.forename: Akio
authors.initials: A
authors.lastname: Mori
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohtomo
authors.forename: Sachie
authors.initials: S
authors.lastname: Maeda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Obase
authors.forename: Mikio
authors.initials: M
authors.lastname: Oka
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000276:immunology* / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D039741:Antigens, Dermatophagoides; C476399:Cd44 protein, mouse; D016207:Cytokines; D018960:Hyaluronan Receptors