Abstract
T-cell responses towards tuberculin (PPD) or the M. tuberculosis-specific antigens ESAT-6 CFP-10 are indicative of prior contact with mycobacterial antigens. In this study, we investigated the exceptional case of a 75-year-old patient who devoted more than one third of his CD4 T-cells against PPD and ESAT-6.
Antigen-specific T-cells were characterised using flow-cytometric intracellular cytokine-staining, ELISPOT-assay, proliferation-assays, and T-cell receptor spectratyping.
T-cell frequencies were far above those found in age-matched controls (median 0.33%, 0.05–6.32%) and remained at high levels for more than two years. The patient initially presented with hemoptysis, but active tuberculosis was ruled out by repeated analysis of sputum and BAL-fluid. Skin-testing was negative and hemoptyses did not have a M. tuberculosis-related etiology. Phenotypical and functional properties of specific T-cells were consistent with a terminally differentiated effector-memory phenotype with capacity to produce IFN-γ, IL-2, and TNF-α. Epitope mapping showed that the CD4 T-cells were directed against a single peptide from ESAT-6 (amino-acid 5-20) that was presented in context of HLA-DR. T-cell receptor Vβ-spectratyping and sequencing of specific CD4 T-cells revealed a prominent peak-fraction of monoclonal origin.
In conclusion, similar to monoclonal gammopathies of undetermined significance (MGUS), this may represent the first T-cell counterpart with known specificity against M. tuberculosis.
- CD4 T-cells
- ESAT-6
- lymphocytes
- monoclonal
- monoclonal gammopathy of undetermined significance
- mycobacterium tuberculosis
- ERS