There has recently been an increase in data indicating that autoimmune mechanisms are involved in the etiopathogenesis of idiopathic thrombocytopenic purpura (ITP) (1, 2). Although antibodies that react with platelets are found in most patients with ITP, the pathogenetic nature of the antibodies remains to be clarified . The discovery of an animal model for ITP has therefore been long-awaited. Here we have found that (NZW x BXSB)Fi (W/B Fi) mice, which develop lupus nephritis with myocardial infarction (3), show thrombocytopenia with age, and that this is due to the presence ofboth platelet-associated antibodies (PAA) and circulating antiplatelet antibodies.Recently, we have demonstrated that allogeneic bone marrow transplantation (ABMT) has curative effects on autoimmune diseases in (NZB x NZW)FI, BXSB, MRL/MP-lpr/lpr (MRL/lpr), and NOD mice (4-6) . These results prompted us to examine whether ABMT can be used to treat ITP. In the present study, we provide evidence that the transplantation of bone marrow from BALB/c mice to W/B F, mice does indeed have preventative and curative effects on ITP
Materials and MethodsMice.Mice ofthe inbred strain BALB/c nu/nu, BALB/c, C57B/6, C3H/HeN, BXSB, NZW were raised under specific pathogen-free conditions in our animal facility. W/B F, males were obtained from the Nippon Shinyaku Research Laboratories, Kyoto, Japan.Staining Procedure andData Analysis.Platelet-rich plasma was obtained as described previously (7) . The platelets were suspended in 1% paraformaldehyde solution for 5 min. After
A small number of B cells are found in the thymus of normal mice. A population of B lymphocytes could be enriched to greater than 90% purity by isolating a low-density fraction on Percoll density gradients and then depleting T cells with a mixture of anti-Thy-1, CD4, and CD8 mAbs and complement. Enrichment was monitored by surface Ig staining and by functional studies (responsiveness to LPS, and to anti-mu plus IL-4). When the phenotype of these B cells was studied by flow cytometry, 60-80% had the phenotype Ly-1+ (CD5), Ia+, B220low (CD45R), and Mac-1+ (CD 11b). In contrast, splenic B cells lacked CD5 and CD11b and expressed higher levels of B220 and Ia antigens. These results indicate that most thymic B cells have the phenotype of the Ly-1 B cell subset, which was identified previously as a trace subpopulation in some peripheral tissues and is thought to play a role in autoantibody formation.
Conjugates of tumor-reactive antibody and toxins (immunotoxins) have been used to eradicate tumor cells in vitro and in vivo. Such immunotoxins are highly effective in killing murine leukemic cells in infiltrated bone marrow and should be useful in the bone marrow rescue approach for the treatment of cancer. Similar immunotoxins injected parentally can help to induce prolonged remissions in leukemic mice, and antigen-containing immunotoxins can induce immunologic unresponsiveness in vitro in normal murine splenocytes. Thus, long-range goals for the parental use of immunotoxins include the killing of cancer cells in vivo and the modulation of the immune response for therapeutic purposes.
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