Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion death. We hypothesize that TRALI requires 2 events: (1) the clinical condition of the patient and (2) the infusion of antibodies against MHC class I antigens or the plasma from stored blood. A 2-event rat model was developed with saline (NS) or endotoxin (LPS) as the first event and the infusion of plasma from packed red blood cells (PRBCs) or antibodies (OX18 and OX27) against MHC class I antigens as the second event. ALI was determined by Evans blue dye leak from the plasma to the bronchoalveolar lavage fluid (BALF), protein and CINC-1 concentrations in the BALF, and the lung histology. NS-treated rats did not evidence ALI with any second events, and LPS did not cause ALI. LPS-treated animals demonstrated ALI in response to plasma from stored PRBCs, both prestorage leukoreduced and unmodified, and to OX18 and OX27, all in a concentration-dependent fashion. ALI was neutrophil (PMN) dependent, and OX18/OX27 localized to the PMN surface in vivo and primed the oxidase of rat PMNs. We conclude that TRALI is the result of 2 events with the second events consisting of the plasma from stored blood and antibodies that prime PMNs. IntroductionTransfusion-related acute lung injury (TRALI) is the leading cause of transfusion mortality in the United States. 1,2 TRALI is the acute onset of noncardiogenic pulmonary edema as documented by chest radiograph and profound hypoxemia, in accordance with the definition of acute lung injury (ALI), that occurs within 6 hours of transfusion. 3,4 TRALI may occur with or without conditions that predispose the patient to ALI, and may be the worsening of pulmonary function in patients with preexisting ALI. 3,4 All blood products have been implicated in TRALI, but components that contain large amounts of plasma are mainly responsible. 5,6 The current incidence of TRALI has been estimated as 1/7900 to 1/1330 in the United Kingdom and the United States with lesser incidences in Europe. [5][6][7][8] Current mortality rates vary from 5% to 35% with the lesser mortality rates predominating. [5][6][7][8] The pathophysiology of TRALI has not been elucidated despite numerous studies. [9][10][11][12][13][14] The first mechanism proposed was the infusion of donor antibodies directed against the HLA class I or granulocyte-specific antigens on the recipient's leukocytes with animal models composed of an in vivo murine model and an isolated, perfused rabbit lung that provided physiologic relevance. [9][10][11][12]14 In addition, the neutrophil (PMN) was proposed to be the effector cell, identical to other forms of ALI and the acute respiratory distress syndrome (ARDS). [9][10][11][12]14 However, look-back studies of donors with specific antibodies directed against HLA or granulocyte antigens demonstrated that the infusion of donor antibodies into a recipient that expressed the cognate antigen resulted in TRALI in a minority of these patients, implying that the clinical condition of the recipient may be important for the d...

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Primary cultures derived from neonatal rat forebrain grow almost entirely as glial cultures, with a large astrocytic preponderance and smaller numbers of oligodendrocytic cells. Although both astrocytic and oligodendrocytic characteristics are acquired in vitro, the origins of both types of glia in primary cultures have not been determined. We tested the hypothesis that glia differentiate in vitro from immature neuroectodermal cells by following the fate of germinal zone cells in primary cultures. A monoclonal antibody that binds GD3 ganglioside was used as a marker for cells of the subventricular zone (SVZ), since antibody binding in newborn rat forebrain could be detected by immunofluorescence only in the SVZ of newborn rats (Goldman et al., 1984). We followed the expression of glial fibrillary acidic protein (GFAP), an astrocytic marker; galactocerebroside (GC), an oligodendrocytic marker; and GD3 during the first several weeks of culture. Both GFAP and GC expression were first detected in cells that bound the GD3 antibody. Astrocytes developed during the first week in vitro; eventually, they lost the ability to bind the GD3 antibody and most became GD3-/GFAP+ cells. In high-density cultures, a population of small cells that resided on top of the astrocytic monolayer retained GD3 expression. GC-antibody binding was first observed in these cells of the upper layer, although it was not readily apparent until the second week of culture. Few GC+ cells were seen in cultures grown at low density, however.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary:Refractory acute lymphoblastic leukemia (ALL) is often incurable, and relapse rates following allogeneic bone marrow transplantation (BMT) remain high. We have reported that patients who develop increased numbers of ␥␦ + T cells soon after BMT are significantly less likely to relapse. We now show in seven donor/recipient pairs that donor-derived V␦1 + CD4 − CD8 − ␥␦ + T cells are activated and proliferate in response to recipient primary ALL blasts. In addition, these cells have been shown to bind and lyse the recipient ALL blasts. Separately, ␥␦ + T cells proliferate poorly or not at all in mixed lymphocyte culture against HLA-mismatched unrelated stimulator cells. These observations suggest that allogeneic ␥␦ + T cells could be an effective immunotherapeutic strategy against refractory disease without the risk of graft-versus-host disease. Bone Marrow Transplantation (2001) 27, 601-606.

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