Mast cells play critical roles in hypersensitivity and in defense against certain parasites. We provide evidence that mouse mast cell survival and growth are promoted by monomeric IgE binding to its high-affinity receptor, Fc epsilon RI. Monomeric IgE does not promote DNA synthesis but suppresses the apoptosis induced by growth factor deprivation. This antiapoptotic effect occurs in parallel with IgE-induced increases in Fc epsilon RI surface expression but requires the continuous presence of IgE. This process does not involve the FasL/Fas death pathway or several Bcl-2 family proteins and induces a distinctly different signal than Fc epsilon RI cross-linking. The ability of IgE to enhance mast cell survival and Fc epsilon RI expression may contribute to amplified allergic reactions.

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IntroductionTumor-induced immune suppression is a fundamental problem in cancer biology and immunotherapy. COX metabolites act as tumor promoters when overproduced (1-3), and recent studies have demonstrated that the COX metabolite prostaglandin E 2 (PGE 2 ) exhibits potent immunosuppressive effects, orchestrating an imbalance between type 1 and type 2 cytokines (4-6). PGE 2 mediates its effects, in part, through G proteincoupled PGE receptors, designated EP1, EP2, EP3, and EP4. Differential expression of these EP receptors mediate the diverse, and often antagonistic, effects of PGE 2 and its analogues on a variety of cell types (7-9). The EP2 receptor regulates the activation and differentiation of mouse B lymphocytes (10), modulates T cell development (11-12), and regulates macrophage cytokine release (13) and postsurgery immune responses (14). The EP2 receptor also plays a key role in the differentiation of macrophage-like osteoclast cells as well as the functional response of osteoclasts to PGE 2 (15). Importantly, PGE 2 has been shown to be a key modulator of DC function, altering cytokine production as well as the I-A d class II cell surface marker (16)(17). Despite data describing the production of PGE 2 by tumors and the expression of the EP2 receptor in specific immune populations, the role of the EP2 receptor in modulation of the host immune response to tumors remains uncharacterized.Previous studies show that COX-2 and PGE 2 can play important roles in tumor angiogenesis (3,18,19). Recent publications show that in Apc ∆716 mice, a mouse model for human familial adenomatous polyposis, homozygous deletion of the gene encoding EP2 decreases the number and size of intestinal polyps through inhibition of tumor angiogenesis (19,20). In this study we determined the role of the EP2 receptor in host-tumor interactions. Unlike the results observed in the Apc ∆716 model, we observed no effect of the disruption of the EP2 receptor on tumor angiogenesis. We then examined the role of the EP2 receptor in T cell function, as well as DC differentiation, and functional responses to tumor challenge. Our data demonstrate an important role for the EP2

IntroductionTumor-induced immune suppression is a fundamental problem in cancer biology and immunotherapy. COX metabolites act as tumor promoters when overproduced (1-3), and recent studies have demonstrated that the COX metabolite prostaglandin E 2 (PGE 2 ) exhibits potent immunosuppressive effects, orchestrating an imbalance between type 1 and type 2 cytokines (4-6). PGE 2 mediates its effects, in part, through G proteincoupled PGE receptors, designated EP1, EP2, EP3, and EP4. Differential expression of these EP receptors mediate the diverse, and often antagonistic, effects of PGE 2 and its analogues on a variety of cell types (7-9). The EP2 receptor regulates the activation and differentiation of mouse B lymphocytes (10), modulates T cell development (11-12), and regulates macrophage cytokine release (13) and postsurgery immune responses (14). The EP2 receptor also plays a key role in the differentiation of macrophage-like osteoclast cells as well as the functional response of osteoclasts to PGE 2 (15). Importantly, PGE 2 has been shown to be a key modulator of DC function, altering cytokine production as well as the I-A d class II cell surface marker (16)(17). Despite data describing the production of PGE 2 by tumors and the expression of the EP2 receptor in specific immune populations, the role of the EP2 receptor in modulation of the host immune response to tumors remains uncharacterized.Previous studies show that COX-2 and PGE 2 can play important roles in tumor angiogenesis (3,18,19). Recent publications show that in Apc ∆716 mice, a mouse model for human familial adenomatous polyposis, homozygous deletion of the gene encoding EP2 decreases the number and size of intestinal polyps through inhibition of tumor angiogenesis (19,20). In this study we determined the role of the EP2 receptor in host-tumor interactions. Unlike the results observed in the Apc ∆716 model, we observed no effect of the disruption of the EP2 receptor on tumor angiogenesis. We then examined the role of the EP2 receptor in T cell function, as well as DC differentiation, and functional responses to tumor challenge. Our data demonstrate an important role for the EP2

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Summary:Reliable markers for megakaryocytic reconstitution after peripheral blood stem cell transplantation (PBSCT) have not been established. To determine a convenient and reliable predictor, we measured the number of megakaryocyte progenitor cells in PBSC grafts by clonogenic and flow cytometric assays. Seventeen patients with hematological and solid malignancies were included in this study. For the clonogenic assay, we used thrombopoietin (TPO) as a growth factor to evaluate the maximum number of megakaryocyte progenitor cells. Using a flow cytometric assay, we examined the expression of platelet glycoproteins on CD34 + cells to count the number of megakaryocyte progenitor cells. We used buffer containing EDTA to prevent platelet adhesion to CD34 + cells and selected CD34 + cells by immunomagnetic beads. The best correlation was observed between the number of CD34 + /CD41a + cells and the time to platelet recovery (P = 0.0205), rather than the total number of CD34 + cells. In addition, a close correlation was observed between the number of CD34 + /CD41a + cells and colony-forming unit megakaryocyte (CFU-MK) (P = 0.0018). These observations suggest that the number of CD34 + /CD41a + cells is the best predictor for platelet reconstitution after PBSCT. Keywords: PBSCT; platelet recovery; CD34; CFU-MK; thrombopoietinAutologous peripheral blood stem cell transplantation (PBSCT) has been increasingly used following high-dose chemotherapy with or without total body irradiation (TBI) for patients with hematologic or nonhematologic malignancies. 1,2 Chemotherapy and/or hematopoietic growth factors have been used to mobilize stem and progenitor cells into blood for transplantation. [3][4][5][6] However, the minimum number of stem cells for engraftment has not been fully elucidated, and the factors which predict the tempo of hematopoietic recovery are also undefined. Several reports have shown a correlation between the number of colony-forming unit granulocyte-macrophage (CFU-GM) and CD34 + cells Correspondence: Dr C Shimazaki, Second Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyoku, Kyoto, 602, Japan Received 22 November 1997; accepted 27 January 1998 and the time to granulocyte recovery. 7-9 As for platelet recovery, few studies have been reported; some have shown that the number of CFU-GM and CD34 + cells correlate with platelet recovery, 7-14 but others have not shown a significant correlation. 15,16 Recently, specific markers for megakaryocyte progenitors such as colony-forming unit megakaryocyte (CFU-MK) and CD34 + /CD41 + or CD34 + /CD61 + cells have predicted platelet engraftment in PBSCT. 13,14,16,17 Thrombopoietin (TPO), the ligand for the c-mpl receptor, has been shown to stimulate the growth of megakaryocyte colonies in vitro. [18][19][20] The number and size of CFU-MK induced by TPO was greater than that induced by any other combination of growth factors, suggesting that TPO may be useful for assaying CFU-MK. 21 Based on these observations, we analyzed th...

We performed the immunophenotyping of 101 patients with B‐cell non‐Hodgkin's lymphoma (B‐NHL) using two‐colour flow cytometry (FCM) and found that lymphoma cells coexpressed at least one kind of T‐cell‐associated antigen (T‐Ag; CD2, CD5, CD7) in 25 patients (24·8%). Among these three T‐Ags, CD5 was the most frequently expressed, in 21 patients (20·8%), followed by CD7, expressed in five patients (5·0%), and CD2, which was expressed in two patients (2·0%). Two kinds of T‐Ag were simultaneusly expressed in three patients (CD2/CD5, CD2/CD7, and CD5/CD7, each expressed in one patient). Concerning the expression pattern of T‐Ag, there were no significant differences between lymph nodes and extranodal organs in the three patients with T‐Ag‐positive B‐NHL (T‐Ag(+) B‐NHL) who were analysed. When comparing the clinical features between T‐Ag(+) B‐NHL and T‐Ag‐negative B‐NHL (T‐Ag(–) B‐NHL), extranodal involvement and higher International Prognostic Index (H and H.I.) were significantly frequent in the former subgroup (P = 0·0119 and P = 0·0302 respectively).

To determine whether a difference in donor source affects the outcome of transplantation for patients with primary myelofibrosis (PMF), a retrospective study was conducted using the national registry data on patients who received first allogeneic hematopoietic cell transplantation (HCT) with related BM (n=19), related PBSCs (n=25), unrelated BM (n=28) or unrelated umbilical cord blood (UCB; n=11). The 5-year OS rates after related BM, related PBSC and unrelated BM transplantation were 63%, 43% and 41%, respectively, and the 2-year OS rate after UCB transplantation was 36%. On multivariate analysis, the donor source was not a significant factor for predicting the OS rate. Instead, performance status (PS) ⩾2 (vs PS 0–1) predicted a lower OS (P=0.044), and RBC transfusion ⩾20 times before transplantation (vs transfusion ⩽9 times) showed a trend toward a lower OS (P=0.053). No advantage of nonmyeloablative preconditioning regimens in terms of decreasing nonrelapse mortality or increasing OS was found. Allogeneic HCT, and even unrelated BM and UCB transplantation, provides a curative treatment for PMF patients.