Image 1_KLRG1+CD28⁻CD57+ Ag85A-specific CD8+ T cells mark a severity-associated terminal-differentiation imprint in pulmonary tuberculosis.jpeg

This phenotype was enriched in active PTB and was associated with clinically relevant features of disease burden, including sputum smear positivity, higher smear grade, lymphocyte imbalance, and severe pulmonary involvement. Patients with severe PTB had higher proportions of this subset than patients with non-severe PTB. In receiver operating characteristic analysis, this phenotype showed exploratory in-cohort discriminative potential for distinguishing severe from non-severe PTB, with an apparent area under the curve of 0.8333 (95% CI, 0.7268–0.9398; P<0.0001); patient-level bootstrap resampling yielded a bias-corrected AUC of 0.8333.</p>Conclusions<p>The accumulation of KLRG1⁺CD28^⁻CD57⁺ Ag85A-specific CD8⁺ T cells is closely associated with active and clinically severe PTB.

Rather than establishing a causal mechanism, these findings identify an antigen-specific, terminal differentiation-associated CD8⁺ T-cell phenotype as a potential translational immune correlate of disease severity in human Mtb infection. Its discriminative ability should be regarded as preliminary and requires external validation in larger, prospective, and independently recruited cohorts.</p>