Robust T cell responses to aspergillosis in chronic granulomatous disease: implications for immunotherapy

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 CD 4 + 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. CD 4‐depleted murine models suggested that the role of T cells might be redundant because resistance to aspergillus infection was conserved in CD 4 + T cell‐depleted mice, similar to wild‐type animals. In contrast, mice depleted of neutrophils alone or neutrophils and CD 4 + 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 CD 4 + T cell response suggest that CD 4 + T cell‐based immunotherapy for this disease is unlikely to be beneficial.