Document Detail


Robust T cell responses to aspergillosis in chronic granulomatous disease: implications for immunotherapy.
MedLine Citation:
PMID:  23763437     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
C R Y Cruz; S Lam; P J Hanley; A S Bear; C Langston; A J Cohen; H Liu; C A Martinez; R A Krance; H E Heslop; C M Rooney; I C Hanson; C M Bollard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  174     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-09     Completed Date:  2013-12-02     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  89-96     Citation Subset:  IM    
Copyright Information:
© 2013 British Society for Immunology.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aspergillosis, Allergic Bronchopulmonary / immunology*,  therapy*
Aspergillus fumigatus / immunology
Cell Line
Cells, Cultured
Granulomatous Disease, Chronic / immunology*,  therapy*
Humans
Immunotherapy, Adoptive* / methods
Membrane Glycoproteins / deficiency,  genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
NADPH Oxidase / deficiency,  genetics
T-Lymphocytes / immunology*,  microbiology*,  pathology
Th1 Cells / immunology,  microbiology,  transplantation
Grant Support
ID/Acronym/Agency:
T32 HL092332/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Membrane Glycoproteins; EC 1.6.3.1/Cybb protein, mouse; EC 1.6.3.1/NADPH Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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