Profiling a diverse spectrum of M. tuberculosis antigen-specific T cell responses in asymptomatic IGRA+ individuals before and after TB preventive therapy 9324

Abstract Description Objective We sought to characterize a cohort of asymptomatic IGRA+ individuals with extensive antigen recognition screening and T cell profiling before and after TB preventative therapy (TPT) to better understand Mtb-specific immune responses during asymptomatic infection. Methods Asymptomatic, HIV- IGRA+ individuals were enrolled at the DeKalb Public Health Refugee Clinic in Atlanta, US to receive TPT (3HP) and followed for 1 year with serial whole blood and PBMC collection every 3 months. A response spectrum assay measuring whole blood IFN-γ responses to 60 different Mtb antigens was measured at each study visit. Results Forty-nine participants were included in this analysis. Of 60 Mtb screening antigens, 15 showed a significant decrease in whole blood IFN-γ response 12 months after starting TPT (-log(FDR) threshold of 1.3). A subgroup of 8 antigens were selected for flow cytometry T cell profiling amongst 12 individuals. Utilizing Phenograph clustering algorithm on cytokine positive CD4 T cells, 8 IFN-γ+ clusters were identified, 4 of which showed significant changes after TPT based on Wilcox paired analysis, including IFN-γ+TNF+HLADR+, IFN-γ+TNF+IL2+CD153+, IFN-γ+TNF+PD1+, and IFN-γ + (monofunctional) clusters. Conclusions Our data demonstrate heterogeneity in antigen recognition among asymptomatic IGRA+ individuals prior to treatment, with detectable shifts in IFN-γ+ T cell phenotypes after treatment. Studies of Mtb-specific T cell transcriptional profiles are ongoing. Funding Sources This project was supported by NIH Tuberculosis Research Unit U19- Grant AI111211. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)