Diminished Interleukin-7 receptor expression on T-cell subsets in tuberculosis patients

Immunopathology in human tuberculosis affects T-cell phenotype and functions. Previous studies identified impaired T-cell sensitivity to Interleukin (IL)-7 accompanied by lower IL-7 receptor α-chain (IL-7Rα) expression in patients with acute tuberculosis. In the present study, we characterized affected T-cell subsets and determined the influence of tuberculosis disease severity and treatment response. Tuberculosis patients (n = 89) as well as age- and gender-matched asymptomatic contacts (controls, n = 47) were recruited in Ghana. Mycobacterium (M.) tuberculosis sputum burden was monitored prior to and during treatment. Blood samples from all patients and controls were analyzed for IL-7Rα expression and T-cell markers by multi-colour flow cytometry. CD4⁺ and CD8⁺ T-cells of tuberculosis patients showed generally lower IL-7Rα expression as compared to controls. Concomitantly, tuberculosis patients had higher proportions of naïve and lower proportions of memory CD4⁺ T-cells. Notably, a subset of CD27 positive central memory T-cells (T_cm), which lacked IL-7Rα expression was enriched in tuberculosis patients as compared to controls. M. tuberculosis sputum burden was not associated with differences in IL-7Rα expression. Treatment duration and response showed no clear effects although IL-7Rα expression patterns were highly variable. These results suggested generally impaired generation of memory CD4⁺ T-cells and enrichment of a T_cm subset without IL-7Rα expression in patients with tuberculosis.