We investigated the expression of an apoptosis associated antigen (Fas) (CD95) on hematopoietic progenitor cells. Freshly isolated CD34+ cells from bone marrow did not express Fas. However, interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) induced dose-dependent expression of both Fas mRNA and Fas protein on the surface of CD34+ cells after 48 hours of serum-free culture. TNF-alpha-induced Fas expression was mediated by p55-TNF-alpha receptor. Induced Fas was functional as it could transduce apoptotic signals in response to anti-Fas monoclonal antibody (MoAb). The Fas-defective 1pr mice are reported to have abnormally radio-resistant hematopoietic stem cells. Consequently, we also investigated the relation between Fas and ionizing radiation. Human CD34+ cells expressed Fas following low-dose ionizing radiation in a dose-dependent fashion. Fas induced on CD34+ cells mediated apoptosis in response to anti-Fas MoAb. We evaluated the expression of Fas and Bel-2 on CD34+ hematopoietic progenitor cells expanded in vitro. CD34+ cells isolated from bone marrow were cultured with hematopoietic growth factors for 7 days. Approximately half of the freshly isolated CD34+ cells expressed Bel-2. CD34+ cells cultured with hematopoietic growth factors gradually became positive for Fas and rapidly lost Bel-2 expression. Furthermore apoptosis was induced in the cultured CD34+ population in response to anti-Fas MoAb. Thus, functional Fas can be induced on hematopoietic progenitor cells in vitro by negative hematopoietic regulators, ionizing radiation, as well as positive hematopoietic regulators. The Fas system is thought to play an important role at the level of hematopoietic progenitor cells in both physiologic and pathologic conditions.

We investigated the role of monocyte/macrophage-activating cytokines in pathogenesis of haemophagocytic lymphohistiocytosis (HLH) in 21 adult patients. Sera from patients with active HLH contained extremely high levels of macrophage colony-stimulating factor (M-CSF) and of interferon-gamma (IFN-gamma). These levels returned to almost normal during remission. Neither interleukin-4 nor granulocyte/macrophage colony-stimulating factor could be detected. Active HLH sera also contained high concentrations of inflammatory monokines, such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). Serum concentrations of soluble CD8 and soluble interleukin-2 receptor were extremely high during active HLH, and returned to virtually normal levels during remission. Circulating CD2+ T-cells obtained from patients with active HLH spontaneously secreted M-CSF and IFN-gamma in vitro, whereas circulating monocytes did not produce detectable levels of both M-CSF and IFN-gamma, but produced high levels of IL-6 and TNF-alpha. These findings suggest that IFN-gamma and M-CSF at least partly from T-cells, such as CD8+ T-cells, might contribute to activation of monocytes or histiocytes, resulting in the up-regulated monokine production and haemophagocytosis in HLH.

Summary:treatment with ganciclovir combined with immune globulin, it remains an important cause of morbidity and mortality after allogeneic BMT. 3-7Cytomegalovirus (CMV) infection and CMV-associated disease were monitored using the CMV antigenemia Major risk factors for CMV infection and CMV-associated disease include seropositivity for CMV before transassay in 72 patients who received allogeneic bone marrow transplantation (BMT), and their incidences were plant and the development of acute graft-versus-host disease (GVHD), which is closely related to genetic disparity compared between related and unrelated donor transplant patients. The incidence of CMV infection after between recipients and donors.

A technique for the rapid detection of cytomegalovirus (CMV) antigen-positive blood leucocytes (CMV antigenaemia) was evaluated in 15 marrow transplant patients as a means of diagnosis and for monitoring CMV-associated disease. CMV antigenaemia was determined by direct immunoperoxidase staining of leucocytes with a peroxidase-labelled monoclonal antibody, HRP-C7, which binds an immediate-early antigen of human CMV. CMV antigenaemia occurred in 7/15 marrow transplant patients (47%) and was initially detected between 4 and 6 weeks after transplantation. CMV-associated diseases developed in 3/15 patients (20%). All patients with CMV-associated disease had a relatively large number of CMV antigen-positive leucocytes, exceeding 10 per 50,000 white blood cells (WBCs). In the remaining 12 patients, CMV antigen-positive leucocytes were less than 10 per 50,000 WBCs or were undetectable. CMV-associated disease did not develop in these patients during the period of monitoring. CMV antigen-positive leucocytes were detected more frequently in patients who developed acute graft-versus-host disease (GVHD) or haemorrhagic cystitis than in those without such complications. CMV antigens were detectable from 1 to 4 weeks before the onset of CMV-associated disease which allowed initiation of ganciclovir treatment at an early stage. The degree of CMV antigenaemia paralleled the clinical symptoms and signs, higher degrees of antigenaemia being associated with more significant disease. Thus, the detection of CMV antigen-positive blood leucocytes is useful for the diagnosis and monitoring of CMV-associated disease following bone marrow transplantation.