T‐cell apoptosis and differential human leucocyte antigen class II expression in human thymus

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Abstract
Relatively little is known of the details of human leucocyte antigen (HLA) expression and thymocyte selection in human thymus. In both humans and mice major histocompatibility complex (MHC) molecules have been described which show a highly restricted thymic expression. Such patterns may offer clues about cellular interactions in thymic selection because transgenic mice with MHC expression targeted to specific thymic sites show altered T-cell receptor (TCR) repertoire selection. We have analysed human thymic HLA class II expression, relating the expression pattern to sites of thymocyte apoptosis. While HLA-DQ is poorly expressed by most peripheral antigen-presenting cells (APC), thymus stains strongly for HLA-DQ as well as for HLA-DR. HLA-DM is abundant in medulla but weakly expressed by cortical cells. Class II expression in Hassall’s corpuscles (HC) is unusual in several respects: we have previously shown them to be encircled by HLA-DO+ epithelial cells and here further demonstrate that HC are negative for HLA-DR and HLA-DP, but often positive for HLA-DQ and HLA-DM. Transcriptional control of HLA class II products at this site is thus unlike cells that have previously been studied. Apoptotic thymocytes are restricted to the cortex and the corticomedullary junction. However, a minority of apoptotic cells are visible in the medulla, these being found in the HLA-DQ positive HC. The apoptotic thymocytes in HC can be CD4+ single positive (SP), CD8+ SP or CD4+CD8+ double-positive (DP). This study thus shows that the HC within human thymic medulla are noteworthy both for their unusual hierarchy of HLA class II expression and because they are the only medullary site of thymocyte apoptosis. We propose that HC are a site at which mature thymocytes receive activation/tolerization signals from peptides reprocessed from apoptotic cells. The differential HLA transcriptional control at this site may indicate that specific T-cell subpopulations are affected.