title: Robust T cell responses to aspergillosis in chronic granulomatous disease: implications for immunotherapy.
abstract: Chronic granulomatous disease (CGD) patients are highly susceptible to invasive aspergillosis and might benefit from aspergillus-specific T cell immunotherapy, which has shown promise in treating those with known T cell defects such as haematopoietic stem cell transplant (HSCT) recipients. But whether such T cell defects contribute to increased risks for aspergillus infection in CGD is unclear. Hence, we set out to characterize the aspergillus-specific T cell response in CGD. In murine CGD models and in patients with CGD we showed that the CD4(+) T cell responses to aspergillus were unimpaired: aspergillus-specific T cell frequencies were even elevated in CGD mice (P < 0·01) and humans (P = 0·02), compared to their healthy counterparts. CD4-depleted murine models suggested that the role of T cells might be redundant because resistance to aspergillus infection was conserved in CD4(+) T cell-depleted mice, similar to wild-type animals. In contrast, mice depleted of neutrophils alone or neutrophils and CD4(+) T cells developed clinical and pathological evidence of pulmonary aspergillosis and increased mortality (P < 0·05 compared to non-depleted animals). Our findings that T cells in CGD have a robust aspergillus CD4(+) T cell response suggest that CD4(+) T cell-based immunotherapy for this disease is unlikely to be beneficial.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, USA.
authors.forename: C R Y
authors.initials: CR
authors.lastname: Cruz
authors.forename: S
authors.initials: S
authors.lastname: Lam
authors.forename: P J
authors.initials: PJ
authors.lastname: Hanley
authors.forename: A S
authors.initials: AS
authors.lastname: Bear
authors.forename: C
authors.initials: C
authors.lastname: Langston
authors.forename: A J
authors.initials: AJ
authors.lastname: Cohen
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: C A
authors.initials: CA
authors.lastname: Martinez
authors.forename: R A
authors.initials: RA
authors.lastname: Krance
authors.forename: H E
authors.initials: HE
authors.lastname: Heslop
authors.forename: C M
authors.initials: CM
authors.lastname: Rooney
authors.forename: I C
authors.initials: IC
authors.lastname: Hanson
authors.forename: C M
authors.initials: CM
authors.lastname: Bollard
mesh_terms: D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology* / Q000628:therapy*; D001232:Aspergillus fumigatus / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D006105:Granulomatous Disease, Chronic / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology / Q000637:transplantation
chemical_list: D008562:Membrane Glycoproteins; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: T cells; chronic granulomatous disease (CGD); therapy/immunotherapy