The effect of IgG levels on the number of natural killer cells and their Fc receptors in chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND AND PURPOSE: High-dose intravenous immunoglobulin (IVIg) is an established treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although Fc receptors on natural killer cells have been suggested as a target for IVIg, the pharmacological effects are not yet clarified. We hypothesize that IVIg therapy, dependent on the plasma IgG level, suppresses the cytotoxic capacity by a reduction in numbers of NK cells and their Fc receptor CD16. PATIENTS AND METHODS: Ten consecutive patients with CIDP in maintenance therapy with IVIg were studied before and immediately after the infusion of 0.7-2.0 g/kg IVIg. Peripheral blood mononuclear cell samples from these patients were analyzed immediately after isolation using flow cytometry and cytotoxicity assays. RESULTS: We found that following IVIg treatment, the cytotoxic activity of NK cells in CIDP patients was suppressed, partly caused by a dose-dependent decline in the number of circulating NK cells. In addition, a dose-dependent blockage of CD16 occurred. CONCLUSIONS: The study implies that IVIg infusion induces a substantial decline in the number of peripheral NK cells and a suppression of NK-cell-mediated cytotoxicity. We propose that these impairments of the NK cells contribute to the therapeutic effect of IVIg in CIDP.

Biodistribution and tumor localization of lymphokine-activated killer T cells following different routes of administration into tumor-bearing animals.

PURPOSE: The efficiency of adoptive cellular immunotherapy of cancer might depend on the number of effector cells that reach the malignant tissues. In the present study, the biodistribution and tumor localization of ex vivo lymphokine-activated T killer (T-LAK) cells was investigated. METHODS: T-LAK cells were labeled with 125I-dU or the fluorescent dye tetramethylrhodamine isothiocyanate (TRITC) and transferred by intravenous, -cardiac, -portal or -peritoneal injection into normal (C57BL/6) mice or mice with syngeneic day-7 to day-12 B16 melanoma metastases established in various organs. The overall biodistribution of the T-LAK cells was measured by gamma counting and their tumor localization by fluorescence microscopy. RESULTS: At 16 h after intravenous injection, the organ distribution of 125I-dU-labeled T-LAK cells was identical in normal and tumor-bearing animals. Fluorescence microscopy of lung tissue from animals receiving TRITC-labeled T-LAK cells revealed, however, a fivefold higher accumulation of T-LAK cells in lung metastases than in the surrounding normal lung tissue (1174 and 226 cells/mm2 respectively). Some pulmonary metastases were, however, resistant to infiltration. Very few intravenously injected cells redistributed to other organs or to tumors in these, since only 60 and 30 T-LAK cells/mm2 were found within metastases of the adrenal glands and the liver respectively. However, following injection of T-LAK cells via the left ventricle of the heart, a threefold increase (from 60 to 169 cells/mm2) in the number of transferred cells in metastases of the adrenal glands was observed. Moreover, following locoregional administration of T-LAK cells into the portal vein, tenfold higher numbers (from 30 to 400 cells/mm2) were found in hepatic metastases than were observed following intravenous or intracardiac injection. In the liver, a surprisingly large number of intraportally injected T-LAK cells (approx. 1300/mm2) were observed to accumulate in the perivascular spaces of the portal, but not the central veins. Even though some superficial ovarian and liver metastases were separated from the peritoneal cavity by only the peritoneal lining, no localization into these metastases was seen following intraperitoneal injection of the T-LAK cells. While treatment of tumor-bearing animals with T-LAK cells plus IL-2 reduced lung metastases by 76% as compared to treatment with IL-2 alone (P<0.03), no significant reduction of liver metastases was seen. CONCLUSIONS: T-LAK cells are able to localize substantially into tumor metastases in various anatomical locations, but mainly following locoregional injection. This finding might have important implications for the design of future clinical protocols of adoptive immunotherapy based on T cells.

Delineation of erythropoiesis in normal and malignant bone marrow using monoclonal antibody AS-E1 directed against transferrin receptors (CD71).

We have delineated the erythropoietic compartment in normal and malignant bone marrow (BM) by using the monoclonal antibody (mAb) AS-E1 directed against the transferrin receptor by flow cytometric (FCM) analysis. In normal BM we found a bimodal expression in antigen density with a minor subset (approximately 3%) expressing AS-E1high and a larger subset (approximately 15%) expressing AS-E1low. By fluorescence activated cell sorting, morphological examination of smears stained by immunocytochemistry and by BFU-E assays the AS-E1high fraction was shown to contain cells of erythroid origin (proerythroblasts, basophilic erythroblasts and polychromatic erythroblasts), whereas the AS-E1low fraction consisted mainly of promyelocytes and myelocytes. In patients with malignant hematological disorders we found a more pronounced heterogeneity in the density and the degree of AS-E1low expression compared to normal BM, and to further characterize the AS-E1low cells in patients and to exclude that this broad reactivity interfered with the identification of the AS-E1high cells, we employed triple-color FCM assays with mAbs directed against the myeloid surface markers CD13 and CD66 in addition to AS-E1. In all patients we found that 80-90% of the AS-E1low cells co-expressed CD13 and/or CD66 and thus were of myeloid origin. Finally, we evaluated 2 methods for determination of the AS-E1high subset and found an assay involving forward light scatter and logAS-E1 density to be sufficient. We conclude that AS-E1high is a valid FCM marker for the normal erythropoiesis.

Sodium hyaluronate and methylcellulose in extracapsular cataract extraction. A controlled study of the intraocular inflammation following the peroperative use of sodium hyaluronate and methylcellulose.

In a controlled prospective trial the peroperative use of sodium hyaluronate and methylcellulose (2%) was compared. Two hundred and fifteen patients received sodium hyaluronate and 189 methylcellulose during extracapsular cataract extraction. We found no significant difference in postoperative anterior chamber inflammation, intraocular pressure, frequency of fibrin in the anterior chamber, nor need for additional medication during the first 5 postoperative days.