T cell vaccination in mice with invasive pulmonary aspergillosis

Aspergillus fumigatus, an opportunistic fungal pathogen, is responsible for multiple airway diseases of an allergic and a nonallergic nature. In a mur ine model of invasive pulmonary aspergillosis, resistance is associated wit h a decreased lung inflammatory pathology and the occurrence of an IL-12-de pendent Th1-type reactivity that are both impaired by IL-4, In the present study we assess the ability of Aspergillus crude culture filtrate Ags and t he recombinant allergen Asp f 2 to induce protective antifungal responses i n mice with invasive pulmonary aspergillosis, Similar to what occurred upon nasal exposure to viable A. fumigatus conidia, treatment of immunocompeten t mice with Aspergillus crude culture filtrate Ags resulted in the developm ent of local and peripheral protective Th1 memory responses, mediated by Ag -specific CD4(+) T cells producing IFN-gamma and IL-2 capable of conferring protection upon adoptive transfer to naive recipients. Protective Th1 resp onses could not be observed in mice deficient of IFN-gamma or IL-12 and did not occur in response to Asp f 2, which, on the contrary, elicited high le vel production of inhibitory IL-4. The results show that Ags of Aspergillus exist with the ability to induce both Th1- and Th2-type reactivity during infection, a finding that suggests a possible mechanism through which poten tially protective immune responses are inhibited in mice with the infection . However, the occurrence of Th1-mediated resistance upon vaccination with Aspergillus crude culture filtrate Ags, suggests the existence of fungal Ag s useful as a candidate vaccine against invasive pulmonary aspergillosis.