CD1-restricted recognition of exogenous and self-lipid antigens by duodenal gammadelta+ T lymphocytes.
Gammadelta T cells are present in the mucosal intestinal epithelia and secrete factors necessary to maintain tissue integrity. Ags recognized by these cells are poorly defined, although in mice non-classical MHC class I molecules have been implicated. Since MHC class I-like CD1 receptors are widely expressed at the surface of epithelial and dendritic intestinal cells and have the capacity to present lipid Ags to T cells, we hypothesized that these molecules might present autologous and/or exogenous phospholipids to intestinal gammadelta T lymphocytes. Intraepithelial T lymphocytes from normal human duodenal mucosal biopsies were cloned and exposed to natural and synthetic phospholipids using CD1a-, CD1b-, CD1c- or CD1d-transfected C1R lymphoblastoid or HeLa cell lines as APCs. Their cytolytic properties and regulatory cytokine secretion were also examined. Most clones obtained from duodenal mucosa (up to 70%) were TCRalphabeta+, and either CD4+ or CD8+, whereas 20% were CD4-CD8- (6 clones) or TCRgammadelta+ (12 clones). A relevant percentage (up to 66%) of TCRgammadelta+ but few (<5%) TCRalphabeta+ T cell clones responded to synthetic and/or natural phospholipids presented by CD1 molecules, as measured by both [(3)H]thymidine incorporation and IL-4 release assays. A Th1-like cytolytic and functional activity along with the ability to secrete regulatory cytokines was observed in most phospholipid-specific gammadelta T cell clones. Thus, a substantial percentage of TCRgammadelta+ but few TCRalphabeta+ from human duodenal mucosa recognize exogenous phospholipids in a CD1-restricted fashion. This adaptive response could contribute to mucosal homeostasis, but could also favor the emergence of inflammatory or allergic intestinal diseases.
Russano
Anna M
AM
Laboratory of Experimental Immunology and Allergy, Section of Internal Medicine and Oncological Sciences, Department of Clinical and Experimental Medicine, University of Perugia Medical School, Perugia, Italy.
Bassotti
Gabrio
G
Agea
Elisabetta
E
Bistoni
Onelia
O
Mazzocchi
Alessandro
A
Morelli
Antonio
A
Porcelli
Steven A
SA
Spinozzi
Fabrizio
F
D017951:Antigen Presentation / Q000235:genetics; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D004382:Duodenitis / Q000276:immunology; D004386:Duodenum / Q000276:immunology*; D006367:HeLa Cells; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D018928:Immunity, Mucosal; D015847:Interleukin-4 / Q000276:immunology; D008055:Lipids / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018949:Antigens, CD1; D001324:Autoantigens; C508598:IL4 protein, human; D008055:Lipids; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4