Massive monoclonal expansion of CD4 T-cells specific for a Mycobacterium tuberculosis ESAT-6 peptide

作者：Hodapp Tobias; Sester Urban; Mack Ulrich; Singh Mahavir; Meier Thomas; Wiech Elisabeth; Fisch Paul; Ehl Stephan; Sester Martina^*

来源：European Respiratory Journal, 2012, 40(1): 152-160.

DOI：10.1183/09031936.00175611

• CD4 T-cells
• early secretory antigenic target 6
• lymphocytes
• monoclonal
• monoclonal gammopathy of undetermined significance
• Mycobacterium tuberculosis

T-cell responses towards tuberculin (purified protein derivative; PPD) or the Mycobacterium tuberculosis-specific antigens early secretory antigenic target (ESAT)-6 and culture filtrate protein-10 are indicative of prior contact with mycobacterial antigens. In this study, we investigated the exceptional case of a 75-yr-old patient who devoted more than one-third of his CD4 T-cells against PPD and ESAT-6. %26lt;br%26gt;Antigen-specific T-cells were characterised using flow cytometric intracellular cytokine staining, ELISPOT assay, proliferation assays, and T-cell receptor spectratyping. %26lt;br%26gt;T-cell frequencies were far above those found in age-matched controls (median 0.33%, range 0.05-6.32%) and remained at high levels for %26gt;2 yrs. The patient initially presented with haemoptysis, but active tuberculosis was ruled out by repeated analysis of sputum and bronchoalveolar lavage fluid. Skin testing was negative and haemoptyses did not have a M. tuberculosis-related aetiology. Phenotypical and functional properties of specific T-cells were consistent with a terminally differentiated effector-memory phenotype with capacity to produce interferon-c, interleukin-2 and tumour necrosis factor-a. 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 Vb-spectratyping and sequencing of specific CD4 T-cells revealed a prominent peak fraction of monoclonal origin. %26lt;br%26gt;In conclusion, similar to monoclonal gammopathies of undetermined significance, this may represent the first T-cell counterpart with known specificity against M. tuberculosis.

• 出版日期2012-7