The evolution of MHC restrictions in antigen recognition by T cells in a haploidentical bone marrow transplant recipient.
We have longitudinally followed the major histocompatibility complex (MHC) restrictions that govern the response of T lymphocytes to specific Ag in a child with severe combined immunodeficiency who was successfully transplanted by using T cell depleted haploidentical maternal bone marrow cells and immunized shortly afterwards with tetanus toxoid (TT) Ag. In the first year post-transplant, monocytes were of both donor and recipient origin whereas T and B cells were of donor origin. Three years after transplant, all monocytes and T and B cells were of donor origin. T lymphocytes taken from the child at that time and depleted in vitro of alloreactivity to paternal Ag proliferated in response to TT presented by maternal as well as paternal monocytes. A TT-specific T cell line established from these cells in the presence of maternal monocytes cooperated with maternal but not with paternal monocytes, whereas a TT-specific T cell line established in the presence of paternal monocytes cooperated with paternal but not with maternal monocytes and with monocytes derived from a paternal uncle who shared the haplotype inherited by the recipient from her father. These results show that long-term memory T cells restricted to recipient MHC Ag not shared with the bone marrow donor continue to circulate long after the disappearance of accessory cells of recipient origin. These T cells could potentially participate in a secondary immune response because they were shown to recognize TT presented by recipient fibroblasts induced to express class II MHC molecules following treatment with IFN-gamma.
Geha
R S
RS
Division of Immunology, Children's Hospital, Boston, MA 02115.
Rosen
F S
FS
D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation; D016026:Bone Marrow Transplantation; D002678:Chimera; D005260:Female; D006681:HLA-D Antigens / Q000235:genetics* / Q000276:immunology; D006238:Haploidy; D006650:Histocompatibility Testing; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000601:surgery; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000637:transplantation; D012150:Polymorphism, Restriction Fragment Length; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D013745:Tetanus Toxoid / Q000276:immunology; D014019:Tissue Donors
D006681:HLA-D Antigens; D013745:Tetanus Toxoid