direct ex-vivo evaluation of pneumococcal specific t-cells in healthy adults直接的体外评价健康成人的肺炎球菌特定的t细胞.pdfVIP

Direct Ex-Vivo Evaluation of Pneumococcal Specific T-Cells in Healthy Adults 1 2 1 Aamir Aslam , Helen Chapel , Graham Ogg * 1 MRC Human Immunology Unit, Oxford NIHR Biomedical Research Centre, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom, 2 Clinical Immunology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom Abstract Streptococcus pneumoniae is an encapsulated bacterium that causes significant global morbidity and mortality. The nasopharynxes of children are believed to be the natural reservoir of pneumococcus and by adulthood nasopharyngeal carriage is infrequent; such infrequency may be due to demonstrable pneumococcal specific T and B-cell responses. HLA Class 2 tetrameric complexes have been used to characterise antigen specific T-cell responses in a variety of models of infection. We therefore sought to determine the frequency and phenotype of pneumococcal specific T-cells, using a novel HLA-DRB1*1501 tetramer complex incorporating a recently defined T-cell epitope derived from the conserved pneumococcal serine/threonine kinase (StkP). We were able to detect direct ex-vivo StkP446–60-tetramer binding in HLA- DRB1*1501 adults. These StkP446–60-tetramer binding T-cells had increased CD38 expression and were enriched in CCR7- CD45RA+ expression indicating recent and on-going activation and differentiation. Furthermore, these StkP446–60-tetramer binding T-cells demonstrated rapid effector function by secreting interferon-gamma on stimulation with recombinant StkP. This is the first study to directly enumerate and characterise pneumococcal specific T-cells using HLA class 2 tetrameric complexes. We fo