Studies of T cells and TCR usage in Sarcoidosis
Sarcoidosis is a multisystem inflammatory disease of unknown etiology. In the majority of patients the lungs and/or intra-thoractic lymph nodes are affected and active disease is characterized by increased numbers of lymphocytes in the lower airways. To gain deeper knowledge of the cause of disease, we use an immunological toolbox of methods. These methods include flow cytometry, ELISpots and ELISAs.
T cells, are central players in cell-mediated immunity. There are almost an infinite number of specificities of TCRs available in the pool of naïve T cells. During immune responses, T cells react to specific antigens presented on APCs. Activation result in clonal expansion of cells with the same TCR specificity. CD4+ T helper cells have a predominant role in sarcoidosis, since diagnosis can be confirmed in 50 -60 % of patients based on an elevated CD4+/CD8+ ratio (>3,5 ).
Elevated numbers of activated T cells are found in bronchoalveolar lavage (BAL) fluid in sarcoidosis patients. HLA-DRB1*0301+ (DR3+) patients, who typically have Löfgren´s syndrome, are characterized by good prognosis and an accumulation of lung CD4+ T cells using the T cell receptor (TCR) gene segment Va2.3 (AV2S3). The corresponding beta-chains that are part of the TCR have until now been poorly characterized, and there is only limited knowledge about the TCR usage in non-acute patients. We study T cells and TCR beta-chain usage in CD4+ and CD8+ T cell subsets in blood and broncoalveolar lavage fluid cells from different sarcoidosis patient groups as well as from healthy control subjects.
Ph.D Kerstin Ahlgren