of the Vetherlands Red Cross Blood rransfusion Service. and lepartment of Pathology., Free Jniversity, Amsterdam, Division of mmunology., Academic Hospital ,eiden, Leiden and Division of mmunologye, Medical Institute of hvironmental Hygiene at Heinrich leine University of Diisseldorf, liisseldorf 1 Introduction Induction of a graft-vs. -host reaction Protection from lethal graft-vs. -host disease by donor stem cell repopulation* Graft-vs.
-host reaction (GVHK) induced in non-irradiated F1 mice with DBA/2J parental spleen and lymph node (LN) cells usually does not lead to acute GVH disease (GVHD). This contrasts with the GVHR induced in other parent-F1 combinations involving both major histocompatibility complex (MHC) class I and class I1 differences between donor and host. Most signs of acute GVHD in non-irradiated F 1 mice relate to immunodeficiency following destruction of the lymphohemopoietic system of the host, which leads to wasting and death due to infections. This sequence of events is prevented when donor lymphoid cells, originating from grafted stem cells, repopulate the destroyed lymphohemopoietic system of the host.To examine whether a "silent" repopulation of the F1 host by donor stem cells might underly the absence of clinical signs of acute GVHD when GVHR is induced with DBA/2J lymphoid cells, GVHR was induced with LN cells, which do not contain stem cells. Indeed, GVHR induced in (C57BL/10 X DBA/2J)F1 (BDF,) mice with 80 x 106 DBA/2J LN cells led to acute GVHD. Signs of acute GVHD such as wasting and death did not occur when donor stem cells, from an inoculum of DBA/2J spleen and LN cells, were allowed to repopulate the lymphohemopoietic system of the host. The effect of donor stem cells on clinical signs of acute GVHD was more apparent when (B10.D2 x DBA/2J)F1, instead of DBA/2J, lymphoid cells were used to induce GVHR. The detection of alloreactive anti-host cytotoxic T lymphocyte (CTL) activity during acute GVHD induced with DBA/2J donor lymphoid cells supports the hypothesis that such CTL contribute to the destruction of the host immune system in acute GVHD.
(GVHR) in nonirradiated F1 mice with parental Tcells may lead to different clinical and immunological syndromes [ 11. Two syndromes, called acute and chronic or lupus-like GVH disease (GVHD), respectively, are distinguished [l-71.
A characteristic sign of acute GVHD is destruction of the host's immune system, which results in severe immunosuppression. Clinical signs associated with acute GVHD include weight loss, anemia, ruffled fur and diarrhea. Immunological signs of acute GVHD comprise low serum Ig, reduced numbers of Ig-producing cells in the spleen, and suppression of the primary immune response to test antigens 18-12]. In addition, donor anti-host CTL can be detected among host spleen cells [6, [13][14][15]. Acute GVHD may lead to death within 3 to 6 weeks after the induction of GVHR (lethal GVHD). Alternatively, the lymphohemopoietic system of the host eventually recovers or becomes [I 95371