Mycobacterium tuberculosis-reactive interferon gamma-secreting T cells are expanded following isoniazid treatment in a Ugandan pediatric cohort 9299

Description Mycobacterium tuberculosis (Mtb) remains a leading cause of infectious disease-related deaths globally, especially in low-resource settings. Pediatric immune responses to Mtb infection have been understudied, owing in large part due to diagnostic challenges in children. We examined T cell responses in a pediatric cohort of Ugandan Mtb-infected children treated with isoniazid (INH), a first-line bacteriolytic antibiotic, hypothesizing that release of bacterial antigen would result in expansion of Mtb-reactive T cells. Mtb-reactive T cells were significantly expanded following INH initiation as measured by cytokine secretion following peptide stimulation. Interferon gamma (IFN-γ) secreting CD8 T cells rose to 9.3% of all circulating CD8 cells at day 7 post-treatment (up from 2.5% at baseline, p = 0.01), and IFN-γ-secreting CD4 cells rose to 6.1% of all circulating CD4 cells (up from 2.6% at baseline, p = 0.005). In particular, a subset of polyfunctional IFN-γ and granzyme B-secreting CD4 cells was also expanded at day 7 (0.9% compared to 0.4% at baseline, p = 0.03). Our work elucidates how bacteriolytic antibiotics may synergize with the immune response to induce anti-Mtb T cell activity. We aim to further characterize and compare the immune response of Mtb-infected children with active and latent disease in an effort to guide diagnostic development.