Charles S. August

Human Chorionic Gonadotropin: Its Possible Role in Maternal Lymphocyte Suppression

Human chorionic gonadotropin completely inhibits the response of lymphocytes to phytohemagglutinin. The effect is both reversible and noncytotoxic. These observations support the theory that the fetus is accepted because human chorionic gonadotropin represents trophoblastic surface antigen and blocks the action of maternal lymphocytes.

Human Chorionic Gonadotropin: Inhibitory Effect on Mixed Lymphocyte Cultures

Human chorionic gonadotropin can inhibit the blast cell transformation of human lymphocytes, both Phytohemagglutinin-induced and in mixed-lymphocyte reactions. This immunosuppression is noncytotoxic,

A hyperimmunoglobulin E syndrome with normal chemotaxis in vitro and defective leukotaxis in vivo

A 26-yr-old male with a lifelong history of atopic dermatitis and recurrent severe staphylococcal abscesses was found to have hyperimmunoglobulinemia E. Evaluation of both the humoral and cellular aspects of chemotaxis in vitro showed both neutrophils and monocytes to be normal. However, quantitative neutrophil migration in vivo was significantly suppressed using the patients own serum as the attractant. This defective migration in vivo was partially corrected by serum from normal donors as the attractant and also partially corrected following plasma infusion in this patient. Evaluation of quantitative leukocyte migration in vivo may be most useful in patients suspected of defects of leukocyte mobility.

Missing Y chromosome in juvenile chronic myelogenous leukemia

SummaryA child with Ph1-negative juvenile chronic myelogenous leukemia (CML) is presented. The only chromosomal abnormality in hematopoietic tissues consisted of an absent Y chromosome. While a missing Y chromosome in adult patients with CML may be associated with a better prognosis, the clinical course in our patient was as malignant as that usually observed in other children with Ph1-negative juvenile CML.This publication is No. 626 from the Department of Biophysics and Genetics, University of Colorado Medical Center.

Improved platelet function following bonemarrow transplantation in an infant with the Wiskott-Aldrich syndrome

Histocompatible bone marrow was transplanted into a 9-month-old boy with Wiskott-Aldrich syndrome. Prior to transplantation, the infant had continuous gastrointestinal bleeding; studies of his platelet function revealed defective abhesiveness to glass and poor aggregation to collagen and adenosine diphosphate. Because the donor was normal in these respects, tests of platelet function were used to follow the progress of the attempted graft. Following the transplant the childs bleeding stopped, platelet adhesiveness became normal, and platelet aggregation improved. The data suggest that improved platelet function was partly responsible for the clinical improvement and that the patient was successfully grafted with thrombopoietic tissue.

Regression of oxymetholone-induced hepatic tumors after bone marrow transplantation in aplastic anemia

Treatment of acquired aplastic anemia with androgens has been occasionally associated with the development of hepatic tumors. We have studied a 13-year-old boy with idiopathic aplastic anemia in whom oxymetholone treatment was associated with a partial hematological remission. Thirty-four months later, however, the patient developed multiple hepatic tumors.

Interaction of Choriocarcinoma Cells and Human Peripheral Blood Lymphocytes: RESISTANCE OF CULTURED CHORIOCARCINOMA CELLS TO CELL-MEDIATED CYTOTOXICITY BY MITOGEN-ACTIVATED LYMPHOCYTES

Cultured choriocarcinoma (Be Wo) cells exist that share many of the morphologic and bio-synthetic properties of normal human trophoblasts. In an attempt to develop a model for the immunologic relationship between a sensitized mother and fetus, we mixed Be Wo cells with mitogen-activated cytotoxic lymphocytes in vitro. Be Wo cells were resistant to the cytolytic effects of the activated lymphocytes despite 24-h exposure and intimate cell-to-cell contact as determined by microscopy. Control target cells, a line of human hepatoma cells, were readily destroyed. Cytotoxicity was measured by determining residual radioactivity of [(3)H]thymidine-labeled target cells after exposure to activated lymphocytes. Employing the quantitative assay, we confirmed the morphologic results and showed that Be Wo and a number of other choriocarcinoma cell lines were resistant to the cytotoxic effects of lymphocytes activated by phytohemagglutinin, pokeweed mitogen, and allogeneic cells in mixed lymphocyte cultures. Moreover, Be Wo cells were resistant to injury over a wide range of killer to target cell ratios. Significant killing of the Be Wo cells occurred only after prolonged exposure (48 and 72 h) to the activated lymphocytes. We suggest that one mechanism that may assist the fetus (or a choriocarcinoma) in its immunologic survival is the intrinsic resistance of trophoblast cells to lymphocyte-mediated cytotoxicity.

868 SPLENIC HYPOFUNCTION OF PATIENTS UNDERGOING BONE MARROW TRANSPLANTATION (BMT)

Five recipients of BMT at the Childrens Hospital of Philadelphia developed late bacterial infections. This prompted us to review our clinical experience seeking evidence for splenic hypofunction in those and other patients (pts). Accordingly, we sought Howell-Jolly bodies (HJB) in peripheral blood smears of 29 pts; performed liver-spleen scans (LSS) in 9 pts with chronic graft-vs-host disease (CGVHD) and/or infection; and reviewed the spleens of 7 pts who died and had autopsies. In our series as a whole, 12 pts developed GVHD (5 acute; 2 chronic; 5 acute and chronic). 7/29 pts developed HJB; 4 of these had GVHD. Four pts receiving LSS showed decreased or absent splenic function; 3 had GVHD. The incidence of HJB or decreased function on LSS was not related to underlying diagnosis or preparative regimen. Lymphoid depletion was evident on all 7 spleens whose histopathology was reviewed: 2 showed total; 3 marked; and 2 moderately depleted lymphoid tissue. Our retrospective data suggest that splenic hypofunction is fairly common in the recipients of BMT, especially in pts with GVHD. Prospective studies performed at regular intervals after BMT will be necessary to define the true incidence of this condition and identify those pts who may need prophylactic antibiotic therapy.

680 RESISTANCE OF CULTURED CHORIOCARCINOMA CELLS TO CYTOTOXIC LYMPHOCYTES

Cultured choriocarcinoma cells (BeWo) exist which share many of the morphologic and biosynthetic properties of normal human trophoblasts.In an attempt to develop a model for the immunologic relationship between mother and fetus, we mixed BeWo cells with mitogen-activated cytotoxic lymphocytes in vitro. Microscopic observations revealed that BeWo cells exhibited a marked resistance to the cytolytic effects of the activated lymphocyte in spite of 24 hour exposure and intimate cell to cell contact. The control target cells, a line of human hepatoma cells, were readily destroyed. A quantitative cytotoxicity assay was devised which involved measuring the residual radioactivity of 3-H-Thymidine prelabeled target cells following exposure to activated lymphocytes. Employing this assay, we confirmed the morphologic results and showed that BeWo cells were resistant to the cytotoxic effects of lymphocytes activated by phytohemagglutinin, pokeweed, and allogeneic cells in mixed lymphocyte cultures. Moreover, BeWo were resistant to injury over a wide range of killer to target cell ratios. Significant killing of the BeWo cells occurred only after prolonged exposure (48 and 72 hours) to the activated lymphocytes. Exposing the target cells briefly to trypsin augmented the killing of control cells but not BeWo. These observations suggest that one mechanism which may assist the fetus (or a choriocarcinoma) in its immunologic survival is the intrinsic resistance of trophoblast to lymphocyte mediated cytotoxicity.