title: Protective immunity against the gastrointestinal nematode Nippostrongylus brasiliensis requires a broad T-cell receptor repertoire.
abstract: The parasitic gastrointestinal nematode Nippostrongylus brasiliensis induces massive expansion of T helper type 2 (Th2) cells in the lung and small intestine. Th2 cells are a major source of interleukin-4 and interleukin-13, two cytokines that appear essential for rapid worm expulsion. It is unclear whether all Th2 cells induced during infection are pathogen-specific because Th2 cells might also be induced by parasite-derived superantigens or cytokine-mediated bystander activation. Bystander Th2 polarization could explain the largely unspecific B-cell response during primary infection. Furthermore, it is not known whether protective immunity depends on a polyclonal repertoire of T-cell receptor (TCR) specificities. To address these unresolved issues, we performed adoptive transfer experiments and analysed the TCR-Vβ repertoire before and after infection of mice with the helminth N. brasiliensis. The results demonstrate that all Th2 cells were generated by antigen-specific rather than superantigen-driven or cytokine-driven activation. Furthermore, we show that worm expulsion was impaired in mice with a limited repertoire of TCR specificities, indicating that a polyclonal T-cell response is required for protective immunity.
authors: Institute for Immunology, Ludwig-Maximilians-University, Munich, Germany.
authors: Alexander
authors: A
authors: Seidl
authors: Marc
authors: M
authors: Panzer
authors: David
authors: D
authors: Voehringer
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009559:Nippostrongylus / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D017206:Strongylida Infections / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018793:Interleukin-13; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007073:Immunoglobulin E