[Graft versus host reaction and hybrid resistance in experimental models and clinical practice]

Abstract

The "F1 hybrid transplantation law" states that F1 hybrids of two unrelated inbred strains of mice accept grafts from either parent strain while neither parent accept grafts from the F1 hybrid. However, there are two notable exceptions to this law. Indeed, parent grafts containing immunologically competent cells (spleen cells, bone marrow etc.) react against the F1 normal hosts in which they are placed. In the absence of a host-versus-graft reaction, the graft-versus-host reaction (GvH) may dominate the field and cause untoward reactions which not only negate any benefit derived from the graft, but also cause significant, and often fatal morbidity of the host, that is, a GvH Disease (GvHD). Furthermore, irradiated F1 mice are refractory to the grafting of parental bone marrow, lymphoma cells and normal lymphocytes because of a restriction by non-co-dominant, besides that of codominant MHC-H2 genes. These non-co-dominant genes have been designated Hh genes for Hybrid histocompatibility and the phenomenon itself, hybrid resistance. The cellular, humoral and genetic mechanisms involved in the GvH and hybrid resistance production are explained and discussed in the first, while in the second section of the present review, their equivalent in three human pathological situations are taken into consideration. We focus in detail on two principal immunologic aspects of human bone marrow transplantation: GvH and hematopoietic engraftment; each one of these immunologic aspects has considerable impact on the course and outcome of marrow transplantation in humans. The allograft implantation between HLA-genetically-identical siblings, HLA-aploidentical family members or HLA-phenotypically identical donor-recipient couples are herewith examined, while the autologous bone marrow rescue approach is not taken into consideration. The outcome of bone marrow transplantation depends not only on the degree of genetic disparity between the donor and the recipient, but also on the underlying disease. Bone marrow transplantation is the therapy of choice for patients with aplastic anemia, severe combined immunodeficiency (SCID) and other genetic and acquired immunodeficiency, some leukemias and a few other diseases, mainly if HLA-genetically-identical siblings are available. However, in many cases such siblings are not available. Therefore, the probability of acute or chronic GvHD or graft rejection increases significantly. The clinical and pathologic manifestations, the prognostic factors, and the treatment and prevention of acute and chronic GvHD are illustrated in detail.(ABSTRACT TRUNCATED AT 400 WORDS)