Abstract
Summary: 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.
Original language | English (US) |
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Pages (from-to) | 89-96 |
Number of pages | 8 |
Journal | Clinical and Experimental Immunology |
Volume | 174 |
Issue number | 1 |
DOIs | |
State | Published - Oct 2013 |
Keywords
- Chronic granulomatous disease (CGD)
- T cells
- Therapy/immunotherapy
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy