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: 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
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 174 Issue 1 Pg. 89-96 (Oct 2013) ISSN: 1365-2249 [Electronic] England
• PMID: 23763437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 British Society for Immunology.

Chemical References

• Membrane Glycoproteins
• Cybb protein, mouse
• NADPH Oxidase 2
• NADPH Oxidases

Topics

• 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 2
• NADPH Oxidases (deficiency, genetics)
• T-Lymphocytes (immunology, microbiology, pathology)
• Th1 Cells (immunology, microbiology, transplantation)