Abstract
Interleukin (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. In this study, 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 derived from pathogens, such as Mycobacterium tuberculosis, Candida albicans, and cytomegalovirus, and to the superantigen Staphylococcus aureus enterotoxin B. We found that IL-7 favored the expansion and, in some instances, the uncovering of pathogen-reactive CD4 T cells, by promoting pathogen-specific interferon-γ, IL-2, and tumor necrosis factor recall responses. Our findings indicate that IL-7 unveils and supports reactivation of pathogen-specific T cells with possible diagnostic, prognostic, and therapeutic significance of clinical value, especially in conditions of pathogen persistence and chronic infection.
Highlights
D RESULTS: We found that IL-7 favoured the expansion and, in some instances, the uncovering of te pathogen-reactive CD4 T cells, by promoting pathogen-specific IFNɣ, IL-2 and TNF recall p responses
To investigate putative effects of IL-7 on pathogen-specific T cells, we first analyzed chronically infected tuberculosis (TB) patients. These were chosen based on clinical history and manifestation of acute Mycobacterium tuberculosis (MTB) infection, positive reaction to the tuberculin skin test (TST) and ability of peripheral blood mononuclear cells (PBMCs) to respond to a stimulation with MHC-II-restricted t MTB-specific promiscuous peptides (MTPs) in IFNɣ ELISPOT assays[31]
We demonstrate that IL-7 supports the in-vitro expansion of human pathogenspecific T cells, favoring and, in some instances, enabling their enumeration and characterization
Summary
HIV-seronegative patients with active TB (clinic and culture confirmed) were recruited at the Clinic of Infectious Diseases, San Raffaele Hospital (Milan, Italy). T DMSO; MTB/Ca-Ag responses) PBMCs. Equal numbers of viable (0.1% Trypan Blue-negative) ip cells were resuspended in complete media (RPMI containing penicillin, streptomycin, glutamine r and 10% FCS –all from ThermoFisherScientific- or autologous serum) with or without human c recombinant IL-7 (50 ng/ml, unless specified otherwise in individual figures; R&D s Systems/Biotechne, Minneapolis, USA) for 7 days. Equal numbers of CFSE-labeled cytokine-cultured cells (0.6x106) were stimulated (6hrs) with unpulsed (nil) or MTP-pulsed (4 μg/ml) autologous irradiated (5000 rad) PBMCs (3x106 cells), in the presence of human anti-CD28-stimulating mAb (2 μg/ml, BD Biosciences). Levels of significance are: *, p≤0.05; **, p≤0.005; and ***, p≤0.0005, unless specified Accepted differently in individual figures
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
