T cell-mediated heterologous immunity to different pathogens is promising for the development of immunotherapeutic strategies. Aspergillus fumigatus and Candida albicans, the 2 most common fungal pathogens causing severe infections in immunocompromised patients, are controlled by CD4 ؉ type 1 helper T (T H 1) cells in humans and mice, making induction of fungus-specific CD4 ؉ T H 1 immunity an appealing strategy for antifungal therapy. We identified an immunogenic epitope of the A fumigatus cell wall glucanase Crf1 that can be presented by 3 common major histocompatibility complex class II alleles and that induces memory CD4 ؉ T H 1 cells with a diverse T-cell receptor repertoire that is cross-reactive to C albicans. In BALB/c mice, the Crf1 protein also elicits cross-protection against lethal infection with C albicans that is mediated by the same epitope as in humans. These data illustrate the existence of T cell-based cross-protection for the 2 distantly related clinically relevant fungal pathogens that may foster the development of immunotherapeutic strategies. (Blood. 2011;117(22):5881-5891)

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This study highlights the importance of functional PMN, T-cell, and NK-cell immunity for the outcome of IA. Larger multicenter studies should address the potential use of NK-cell counts for the management of antifungal therapy.

These findings may form the basis for adoptive T-cell transfer for prophylaxis or treatment in patients with these devastating infections.

Highlights d IFN-l induces long-lasting and cell-type-specific gene expression in B cells d IFN-l raises the expression of mTORC1, MYC, and inflammatory-response-related gene sets d IFN-l increases cell-cycle progression in B cells upon BCR activation d IFN-l enhances plasmablast differentiation upon BCR activation