title: Lack of IL-4 receptor expression on T helper cells reduces T helper 2 cell polyfunctionality and confers resistance in allergic bronchopulmonary mycosis.
abstract: T helper (Th)1 and Th2 cells play decisive roles in the regulation of resistance vs. susceptibility to pulmonary cryptococcosis. To study the function of interleukin (IL)-4 receptor (IL-4R) on Th cells in pulmonary cryptococcosis, we infected mice specifically lacking IL-4Rα on CD4(+) T cells (Lck(Cre)IL-4Rα(-/lox) mice) and IL-4Rα(-/lox) controls. Lck(Cre)IL-4Rα(-/lox) mice developed enhanced resistance accompanied by reduced pulmonary allergic inflammation and diminished production of the Th2 cytokines IL-4, IL-5, and IL-13 as compared with IL-4Rα(-/lox) mice. Polyfunctional antigen-specific Th2 cells producing simultaneously two or three Th2 cytokines were reduced in infected Lck(Cre)IL-4Rα(-/lox) mice, pointing to a critical role of polyfunctional Th2 cells for disease progression. Reduced Th2 polyfunctionality was associated with fewer pulmonary alternatively activated macrophages. This work is the first direct evidence for a critical contribution of the IL-4R on Th cells to Th2-dependent susceptibility during allergic bronchopulmonary mycosis. Moreover, the data demonstrate that the quality of the Th2 response has an impact on type 2 inflammation. The analysis of polyfunctional Th2 cells may be useful for monitoring the course of the disease.
authors.affiliation: Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Müller
authors.forename: D
authors.initials: D
authors.lastname: Piehler
authors.forename: W
authors.initials: W
authors.lastname: Stenzel
authors.forename: G
authors.initials: G
authors.lastname: Köhler
authors.forename: O
authors.initials: O
authors.lastname: Frey
authors.forename: J
authors.initials: J
authors.lastname: Held
authors.forename: A
authors.initials: A
authors.lastname: Grahnert
authors.forename: T
authors.initials: T
authors.lastname: Richter
authors.forename: M
authors.initials: M
authors.lastname: Eschke
authors.forename: T
authors.initials: T
authors.lastname: Kamradt
authors.forename: F
authors.initials: F
authors.lastname: Brombacher
authors.forename: G
authors.initials: G
authors.lastname: Alber
mesh_terms: D000818:Animals; D003453:Cryptococcosis / Q000150:complications / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000472:pathogenicity; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000209:etiology / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008262:Macrophage Activation / Q000235:genetics; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014774:Virulence
chemical_list: D016207:Cytokines; D019948:Receptors, Interleukin-4