Immunoglobulin E (IgE) is central to the induction of allergic diseases through its binding to the high-affinity receptor (Fc epsilon R1) on mast cells and basophils. Crosslinking by allergens of the bound IgE leads to the release of various inflammatory mediators. IgE production by B cells requires a physical interaction with T cells, involving a number of surface adhesion molecules, as well as the soluble factors interleukin-4 (IL-4) and IL-13 (ref. 5) produced by T cells, basophils and mast cells. Here we report that, in the presence of IL-4, mast and basophilic cell lines can provide the cell contact signals that are required for IgE synthesis. The human cell lines HMC-1 (mast) and KU812 (basophilic) both express the ligand for CD40 (CD40L) which is shown to be responsible for the IgE production. Moreover, freshly isolated purified human lung mast cells and blood basophils are also shown to express CD40L and to induce IgE production. This evidence suggests that mast cells and basophils may therefore play a key role in allergy not only by producing inflammatory mediators, but also by directly regulating IgE production independently of T cells.

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SUMMARYMast cells (MC), blood basophils (Ba) and moncoytes (Mo) are of haemopoietic origin. Lineagerelationships and transdifferentiation between MC and Mo, or MC and Ba, have been considered, based on common expression of antigens. In this study, comparative phenotypic analyses on MC, Ba and Mo and on respective cell lines were performed using monoclonal antibodies (mAb) to previously defined and novel CD antigens (CD1-130). By cluster analysis, the overall (all 130 CD) phenotypic relationships (given as similarity indices, SI), between primary cells (MC, Ba and Mo) and corresponding cell lines (HMC-1, KU-812, U937) were 0 . 716, 0 . 779 and 0 . 757, respectively. When primary cells were compared, lower SI values were found (MC versus Ba, 0 . 509; MC versus Mo, 0 . 625; Mo versus Ba, 0 . 698). More distant relationships were found between MC versus Ba and MC versus Mo, compared with Ba versus Mo, for adhesion receptor (R)-, complement R-and cytokine R profiles. Analysis of cytokine R revealed most significant dissimilarities between MC versus Ba and MC versus Mo (SI < 0 . 2). Moreover, in contrast to other CD subgroups and other lineages, MC and HMC-1 differed from each other in cytokine R expression (SI 0 . 286). Cytokine R detectable on HMC-1 but not MC were granulocyte-macrophage colony-stimulating factor (GM-CSFR)a(CD116), CD40, Apo-1/ FAS(CD95) and gp130(CD130). Cytokine R detectable on Ba but not MC, were interleukin-3 (IL-3)Ra(CD123), IL-1RII(CD121b), IL-2Ra(CD25) and CD40. In summary, MC, Ba and Mo display a unique CD profile with MC being the most distantly related cell. The most significant mismatch within a given lineage is the loss of cytokine R on mature MC as compared with normal myeloid progenitors and HMC-1 cells.

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Summary:published 1,2 regarding leukemia relapse after BMT which summarize strategies for prevention and treatment of leukemia relapse after BMT. In these articles, treatment for leuTo assess the consequence of second BMT (BMT2) for leukemia relapse after allogeneic BMT, we analyzed the kemia relapse was analyzed in four parts; reinduction chemoradiotherapy, cytokine therapy, donor leukocyte clinical course of 66 recipients who were treated by BMT2 in Japan. Diagnoses included 29 ANLL, 27 ALL, transfusion, and second allogeneic BMT (BMT2). The rate of achieving complete remission by reinduction chemosix CML and four MDS. Durations between the first BMT (BMT1) to relapse and BMT1 to BMT2 were therapy ranged from 30 to 50% in acute leukemias and the median duration of remission was very short, between 6 13.5 ± ± ± 13.7 months and 17.4 ± ± ± 13.9 months, respectively. Donors for BMT2 were replaced in 11 cases. Thirty-one and 14 months. 3 The response to interferon-␣ and donor leukocyte transfusion was good only for chronic phase patients were in CR (or CP) at BMT2. Earlier deaths were observed in those who received BMT2 within 12 CML and poor during the acute phase of CML and acute leukemia. 4 Therefore, BMT2 may be the only hopeful treatmonths after BMT1, mostly caused by regimen-related toxicity and infections. Overall leukemia-free survival ment for leukemia relapsing after BMT. There are many reports 5-8 concerning BMT2 which show rate was 28% at 2 years and 16% at 4 years. Factors influencing the poor prognosis after BMT2 were early 8-76% disease-free survival depending on the diagnosis, disease status, and many other factors which may affect (Ͻ6 months) relapse, early (Ͻ12 months) BMT2, not in remission at BMT2, and ALL. Intensified conditioningoutcome. In order to analyze the current status of second BMT in Japan, we performed a retrospective survey of did not affect either remission duration or LFS. Among the 39 cases observed for more than 100 days, 18 BMT2 for leukemia relapse in BMT units in Japan. We report the results from analysis of multi-institutional experideveloped chronic GVHD (cGVHD) and showed longer remission duration than those without cGVHD. Our ences of repeated BMT. analysis indicates that BMT2 as treatment for leukemia relapse is effective in selected cases, and exploration of pre-BMT treatment and post-BMT immunotherapy is Materials and methods warranted.