Fungus-reactive T cells as Sensitive and Specific Sensors to Diagnose Fungal Infections in Cystic Fibrosis Patients

Cystic fibrosis (CF) patients frequently suffer from chronic infections of the lung, resulting in substantial disease exacerbation. Environmental fungi play a major role in this process as infecting pathogens. The clinical relevance of fungal pathogens ranges from colonization of the lung to sensitization of the immune system to even invasive fungal infections. The major bottleneck for timely and specific treatment of CF patients is the lack of sensitive and specific diagnostic tools allowing differentiating between fungal species and stages of fungal diseases. T lymphocytes are specific sensors for invading pathogens. By using ARTE (antigen-reactive T cell enrichment) for the characterization of antigen-reactive T cells directly from human peripheral blood, we show that fungus-specific CD4+ T cells in CF patients strongly differ in their phenotype and function as compared to healthy donors. Patients with CF can further be sub-classified according to fungus-specific T cell phenotype which can be correlated with clinical parameters. In particular, we show that increased frequencies of fungus-reactive T cells can be used as a specific diagnostic parameter for invasive fungal infections in CF patients. These data imply that the characterization of fungus-specific CD4+ T cells is a valuable tool to resolve the contribution of various specific fungal pathogens to the disease state in individual patients with CF. This approach will help to determine the role of specific fungal pathogens to CF disease exacerbations and will improve diagnosis and prognosis of fungal infections.