Severity of pulmonary lesions and bacillary load in multidrug-resistant tuberculosis is highly related to the senescence status and the exhaustion of T cells

IMPERIALE B; GARCIA ANA; MORACHO LUCILA; GONZALEZ MONTANER PABLO; PALMERO DOMINGO; MORCILLO N; DE LA BARRERA SILVIA

DAVOS

Congreso; World Immune Regulation Meeting XV 2021; 2021

In chronic infection as Tuberculosis (TB), antigen specific T cell dysfunction and up regulation of inhibitory receptors such as programmed celldeath protein (PD1) and expression of CD57 have been associated topersistent antigen stimulation. The aim of this study was to evaluatethe senescence status of T cells in multidrug resistant (MDR TB) andfully drug susceptible (STB) TB patients. All patients showed radiological pulmonary disease (MDR TB: 76% bilateral, 24% unilateral cavities;STB: 53% bilateral, 47% unilateral cavities). All S-TB and 92% MDR TBpatients were smear positive.Peripheral blood samples were obtainedfrom TB patients and healthy donors (MDR TB, n: 59; STB, n: 27; HD,n: 25). Mononuclear cells were isolated and cultured alone or with gamma-irradiated Mtb strains. Expression of senescent markers, CD57 andPD1, were determined by flow cytometry in CD4 and CD8 T cells. Datarecovery from patients included severity of lesions, smear examination,cultures and drug-susceptibility testing. Results showed that MDR-TBpatients had a marked increase of PD1+ and CD57+ expression withinCD4+ and CD8+ T cells compared to STB. Besides, MDR TB patientswith bilateral cavities showed the highest percentage of PD1+ cells inCD4+ and CD8+ subsets. Given that MDR TB patients expend moretime to access to an effective anti TB treatment until the diagnosis ofdrug-resistance, the persistent high bacillary load could promote an excessive exhaustion of memory T cells. And the high expression of senescent T cells in MDR TB could be related with a low specific Th cellresponse observed in MDR-TB patients with severe lung damage and/orpersistent bacillary load.