MHC class I restriction in DiGeorge anomaly patients after allogeneic thymus transplantation (141.22)

Abstract

Abstract Purpose: The aim of this study is to determine whether antigen specific T cells are restricted to host or donor MHC after human allogeneic thymus transplantation for complete DiGeorge anomaly. Methods: Tetramers composed of HLA-A*0201, B*0801, or B*0702 with an Epstein Barr virus (EBV) peptide or HLA-B*0702 with a respiratory syncytial virus (RSV) peptide were used in flow cytometry to detect CD8 T cells restricted to these specificities. After thymus transplantation, DiGeorge anomaly subjects were screened and identified for infection by EBV and RSV. Healthy adults serologically positive for EBV or RSV were identified. EBV and RSV specific CD8 T cells were detected by flow cytometry. Results: We found binding of recipient CD8 T cells to tetramers in 4 of 4 subjects with host HLA:EBV peptide and in 1 subject with host HLA:RSV peptide after thymus transplantation. Donor-restriction was not seen in 5 of 5 subjects receiving thymus unmatched for the tested specificity. This implies that host cortical epithelium is present in the donor thymus to effect host selection, that host selection can occur on cell types other than cortical epithelium (such as on thymocytes), or that host selection can result from initial restriction on totally disparate MHC molecules on donor cortical epithelium. We are assessing host HLA expression in thymic epithelial cell cultures derived from allograft biopsies. The presence of host thymic epithelium could explain the HLA restriction to host seen in the tetramer studies. This study was supported by NIH grant R01 AI 47040 and grant FD-R-002602 from the FDA Office of Orphan Products Development.