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- Title
Robust T cell responses to aspergillosis in chronic granulomatous disease: implications for immunotherapy.
- Authors
Cruz, C. R. Y.; Lam, S.; Hanley, P. J.; Bear, A. S.; Langston, C.; Cohen, A. J.; Liu, H.; Martinez, C. A.; Krance, R. A.; Heslop, H. E.; Rooney, C. M.; Hanson, I. C.; Bollard, C. M.
- 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.
- Subjects
ASPERGILLOSIS treatment; CHRONIC granulomatous disease treatment; T cells; IMMUNOTHERAPY; HEMATOPOIETIC stem cell transplantation; ASPERGILLOSIS; LABORATORY mice; DISEASE risk factors
- Publication
Clinical & Experimental Immunology, 2013, Vol 174, Issue 1, p89
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/cei.12156