BACKGROUND: IL-7 promotes the generation, expansion and survival of memory T cells. Previous mouse and human studies showed that IL-7 can support immune cell reconstitution in lymphopenic conditions, expand tumor-reactive T cells for adoptive immunotherapy and enhance effector cytokine expression by autoreactive T cells. Whether pathogen-reactive T cells also benefit from IL-7 exposure remains unknown. METHODS: Here we investigated this issue in cultures of peripheral blood mononuclear cells (PBMCs) derived from patients infected with various endemic pathogens. After short-term exposure to IL-7, we measured PBMC responses to antigens (Ag) derived from pathogens, such as Mycobacterium tuberculosis (MTB), Candida albicans (Ca) and Cytomegalovirus (CMV), and to the superantigen Staphylococcus aureus enterotoxin B (SEB). RESULTS: We found that IL-7 favoured the expansion and, in some instances, the uncovering of pathogen-reactive CD4 T cells, by promoting pathogen-specific IFNɣ, IL-2 and TNF recall responses. CONCLUSIONS: Our findings indicate that IL-7 unveils and supports re-activation of pathogen-specific T cells with possible diagnostic, prognostic and therapeutic significance, of clinical value especially in conditions of pathogen persistence and chronic infection.