Immunity to human haematopoietic stem cells.

Abstract

Graft rejection is an important problem in human bone marrow transplantation, with a 25–60% incidence in grafts between HLA–identical siblings1–6. In mice, two models of rejection of bone marrow grafts have been described: T-lymphocyte-mediated immunity and hybrid resistance (for reviews see refs 7, 8). The first model involves the recognition of foreign histo-compatibility (H–2) antigens by selected subsets of T lymphocytes. These antigen-reactive cells undergo clonal expansion and differentiate into cytotoxic effector cells which mediate graft rejection. In the hybrid resistance model, mononuclear cells, probably identical to natural killer (NK) cells, react against haematopoietic histocompatibility antigens on parental marrow cells9. Cells involved in hybrid resistance exhibit ‘spontaneous’ cytotoxicity to disparate haematopoietic cells and, in contrast to T-lymphocyte-mediated immunity, do not require a sensitisation phase before differentiating into cytotoxic effector cells. The mechanism of graft rejection following bone marrow transplantation in man is unknown. In transplants between HLA-identical siblings the target antigens of graft rejection are not HLA or antigens closely linked to the major histocompatibility complex (MHC). To study the problem of graft rejection in man we developed and describe here an in vitro model to detect immunity to haematopoietic stem cells committed to granulocyte–macrophage differentiation (CFU-C; colony-forming unit culture). We found that human peripheral blood and bone marrow but not thymus contain a population of cells which are cytotoxic to haematopoietic stem cells following in vitro sensitisation. The effector cell population is not a conventional T or B lymphocyte, monocyte–macrophage or NK cell.