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Acute infectious mononucleosis (IM) is a lymphoproliferative disease caused by the Epstein-Barr virus (EBV) infection. It has been reported that soluble T cell antigens are released from cells in response to T cell activation. In the present study, we investigated whether soluble antigen levels of CD2, CD4 and CD8 in serum increase during acute IM. Soluble CD2, CD4 and CD8 levels in serum were measured by a sandwich enzyme immunoassay. In addition, peripheral blood T cell subsets were analyzed by single and two color flow-cytometric analyses in IM. Patients with IM had increased levels of soluble CD2, CD4 and CD8 in serum samples obtained during acute stages. We found a positive correlation between serum levels of soluble CD8 and absolute counts of HLA-DR+CD8+T cells during acute IM. In addition, the correlation between soluble CD8 levels and serum GOT or GPT levels was shown to be positive during acute IM. Our findings suggest that the soluble antigen levels of CD2, CD4 and CD8, in particular CD8, in serum are an important immunologic parameter for determining the activation of T cells during acute IM.

Inversion of chromosome 16 was found in a 73-year-old female with acute myeloblastic leukemia (FAB:M2). Complete remission was achieved by combined chemotherapy (DNR, Ara-C, 6-MP, Prednisolone), but she relapsed 6 months later without CNS involvement and died of respiratory failure presumably due to cerebrovascular accident during remission reinduction chemotherapy. Biphenotypic surface markers (CD2+ and CD13+) were observed on relapse. Eosinophilia was not observed throughout. Our patient and the other reported case suggest that biphenotypism and the lack of eosinophilia and monocytosis in inv (16) leukemia may be correlated with a poor prognosis.

Technetium-99m diethylene triamine pentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed receptor-binding radiopharmaceutical, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of hepatocytes. Clinical utility of TcGSA was evaluated in 3 control subjects with normal livers and in 54 patients with various liver diseases. The parameter, Receptor Index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus heart at 15 min after the intravenous injection of 3 mg of TcGSA. Receptor concentration ([R]o) was obtained by kinetic analysis of liver and heart time-activity data using pharmacokinetic nonlinear modeling. Values for the Receptor Index and [R]o was statistically different in the control subjects and in patients with mild, moderate, and severe liver diseases. Good correlations were obtained between the Receptor Index, [R]o and conventional liver function tests, such as Child-Turcotte criteria score, prothrombin time, and indocyanine green test. Receptor Index and [R]o were properly estimated even in patients with obstructive jaundice or remarkable portocaval shunt. These data suggest that the receptor imaging as well as its parameters, Receptor Index and [R]o, is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.

A 33-year-old man was hospitalized because of thrombocytopenia and severe splenomegaly. On admission 78% of peripheral lymphoid cells were abnormally large, with pale cytoplasm. Flow cytometry of the abnormal lymphocytes showed that they expressed CD 2, CD 3, CD 11, CD 16, and CD 56, but not CD 4 nor CD 8, so they were T-cell large granular lymphocytes (T-LGL). Abnormal lymphocytes obtained from a lymph node expressed CD 2, CD 16, CD 38, and CD 56, but not CD 3, CD 4, and CD 8, so they were natural killer(NK) cells. Splenectomy was performed and the operative specimen showed diffuse infiltration of pleomorphic lymphocytes, probably chronic lymphocytic leukemia cells. After splenectomy, the platelet count returned to normal but the lymphocytosis continued. Two years after discharge, chemotherapy was done because of thrombocytopenia and hepatomegaly. The patient died of disseminated intravascular coagulation arising from sepsis. The differences and similarities between peripheral and lymph-node lymphocytes suggest that LGL and NK cells may be differentiated from the same kind of cell, somewhat differentiated from stem cells.

[Tc-99m] Galactosyl-neoglycoalbumin (TcNGA) is a synthetic radiolabeled ligand specific to the hepatocyte receptor, hepatic binding protein (HBP), a specific receptor to serum asialoglycoprotein. A TcNGA study was performed on 34 humans: normal volunteers (7) chronic hepatitis (6), hepatic cirrhosis (8), and hepatocellular carcinoma superimposed on cirrhosis (13). Heart and liver time activity curves were obtained following intravenous injection of TcNGA (5 mCi, 1.82 x 10(-9) mol/kg). HBP concentration ([HBP]) was calculated by curve-fitting techniques using the nonlinear three compartment model, which includes biomolecular reaction between HBP and TcNGA. [HBP] values were compared with conventional liver function tests. [HBP] had a good correlation with prothrombin time (n = 34, r = 0.694, p = 0.0001) thrombotest (n = 34, r = 0.692, p = 0.0001), hepaplastin test (n = 26, r = 0.787, p = 0.0001), albumin (n = 34, r = 0.712, p = 0.0001), cholinesterase (n = 34, r = 0.801, p = 0.0001), ICGR15 (n = 33, r = 0.761, p = 0.0001), KICG (n = 30, r = 0.709, p = 0.0001), ICG Rmax (n = 12, r = 0.735, p = 0.0064) and Child-Turcotte classification score (n = 34, r = 0.819, p = 0.0001). We concluded that excellent correlations of [HBP] to conventional liver function tests suggest that in vivo receptor measurement via TcNGA kinetic analysis is a sensitive and promising method in the estimation of hepatic functional reserve in patients with chronic liver disease.

Abnormal expansion of large granular lymphocytes (LGLs) was observed in peripheral blood and bone marrow in a 28-year-old man. He had general lymphadenopathy and splenomegaly. Surface phenotypical analysis of LGLs showed that these LGLs express CD 2, Ia and NKH-1 but not express CD 3, CD 4, CD 8 and Leu 7. Cytochemical analysis of these LGLs revealed positive acid phosphatase and beta-glucuronidase reaction but negative alpha-naphthyl acetate esterase reaction. These LGLs showed very weak NK activity against only MOLT-4 but showed no cytotoxic activity against K 562. An beta-receptor gene rearrangement of human T-cell receptor was not found by Southern blot analysis. Rapid and fetal clinical course with the results of theses analytical studies showed that this case is highly suggestive of acute leukemia of LGLs which is committed to NK cell lineage.

A 55-year-old woman was first seen in October 1986, because of splenomegaly, moderate anemia and leukocytosis. The hemoglobin was 8.8 g/dl, platelet count 24.4 X 10(4)/microliters, and the white cell count 23,800/microliters with 73% atypical lymphoid cells. The bone marrow nucleated cell count was 99,000/microliters with 36% lymphoid cells. These atypical lymphoid cells showed hairy appearance under phase-contrast microscopy, and were positive for tartrate-resistant acid phosphatase. These cells showed the surface phenotype of CD10, CD19, CD20, Leu M5, HCM, and IgG K. Biochemical data revealed marked polyclonal hypergammagloburinemia (PHG) of IgG type (IgG 8756 mg/dl). To elucidate the mechanism of the PHG, we investigated whether hairy cells produce interleukin 6 (IL-6) and express IL-6 receptor. The culture supernatant of these hairy cells increased 3H-thymidine uptake of a IL-6 dependent hybridoma clone (MH60) in a dose-dependent manner. These cells were stained with anti-IL-6 antibody using immuno-cytochemical technique. Our results suggested that these hairy cells produce and secrete IL-6. Immunocytochemical staining with anti IL-6 receptor antibody and the binding assay with 125I-labelled recombinant IL-6 revealed that these cells express little or no receptors for IL-6. It was therefore suggested that IL-6 produced by hairy cells in this case is not an autocrine growth factor for these cells but may play a role in development of PHG by stimulating normal B lymphocytes to produce an excessive amount of immunoglobulin.

It has recently been shown that human T-cell subpopulation can be identified functionally via surface receptors for Fc fragment of immunoglobulins. We detected peripheral blood T-cells bearing the Fc receptor for IgG molecules (T gamma cell) in patients with brain tumors who manifested a variety of immunological abnormalities. We also analyzed immunological values of T gamma cells which were thought to be suppressor and/or a part of killer T cells, comparing with other immunological parameters. The percentage of T gamma cells was significantly higher in patients with malignant brain tumors than in normal controls (6.54 +/- 1.6%). The values of T gamma cells in patients with glioma, metastatic brain tumor, benign brain tumor were 15.4 +/- 4.8%, 14.9 +/- 3.2%, and 8.1 +/- 3.7%, respectively. In the patients with glioma, the values increased in the uncontrolled group compared with the well-controlled group. Furthermore, the values were decreased by surgical removal of the tumor. On immunological study of T gamma cells in the patients with glioma, there was a definite correlation between the values of T gamma cells and ADCC activity. Furthermore, the T gamma cells in the patients showed higher ADCC activity than in normal controls. The values of T gamma cells also correlated with blastogenesis of the peripheral blood lymphocytes by PHA (r = -0.742, p less than 0.001) and Con A (r = -0.662, p less than 0.001). These results suggest that T gamma cells are playing two important roles in patients with glioma such as suppressor function and ADCC activity, and that these cells may change according to the tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)

T cells bearing IgG Fc receptors (Tr cells) were determined in 40 cases of brain tumor using the double rosette method, and compared with the changes of PHA reaction, immunoglobulin (IgG A M), performance status, and mass effect on CT in 20 pre-and post-operative and/or radio-clinico-immunotherapeutic patients. The proportion of control Tr cells was 8-19% in 20 healthy adults. Values of Tr cells over 20% were correlated with a poor grade of performance status, and large mass effects on CT. Post-therapeutic change in the value was well correlated with change in performance status, mass effects, and IgG. Our results suggest a correlation between the value of Tr cells and clinico-radiological findings. Immunological analysis of Tr cells serves as a parameter of tumor expansion or prognosis, and could be of significant importance clinically.

Immunohistochemical study with various monoclonal antibodies against the mononuclear cell surface antigen was performed on the regional lymph nodes of gastric cancer through Avidin-Biotin Complex (ABC) method. In the paracortical area (P.C.) of those lymph nodes without the metastasis of gastric cancer, T cells were dominant, and OKT3 positive (OKT3+) cells and OKT4+ cells were diffusely present, while OKT8+ cells were occasionally recognized. In the sinus, subsets of the above T cells, and OKT9+ cells and OKT10+ cells were observed. In the germinal center (G.C.), mantle zone (M.Z.) and primary follicle (P.F.), which were B cell regions, OKIa1+ cells and Leu12+ cells were diffusely present. OKB7+ cells, OKT9+ cells, OKT10+ cells and Leu7+ cells were also noted in G.C.. Leu8+ cells were observed in M.Z. and P.F.. OKIa1+ cells were occasionally noted in P.C. and sinus. In the lymph nodes with the metastasis, decrease of OKT4+ cells and increase of OKT8+ cells were noted in comparison to the lymph nodes without the metastasis. Using the tissue double fluorescence staining method, it was found that about half of the OKT4+ cells were helper T cells. The majority of OKT8+ cells were identified as cytotoxic T cells or their precursors. By preoperative endoscopic administration of OK-432 or PSK into the tumor, the IL-2 receptor+ cells, or OKM1+ cells and OKT4+ cells increased in the regional lymph nodes and the antitumor activity was intensified.

In gastric cancer patients the proliferative response of T gamma cells to phytohemagglutinin and Pokeweed mitogen was depressed, while that to Concanavalin-A was maintained as compared with that in T non-gamma cells. T gamma cells were activated by Concanavalin-A to suppress the proliferative response of responder cells. Furthermore, T gamma cells from gastric cancer patients contained the suppressor cells which had been already activated in-vivo. On the other hand, natural cell mediated cytotoxic activities of T gamma cells were greater than those of T non-gamma cells. Thus, it is likely that T gamma cells consisted of the heterogenic populations, containing the suppressor and cytotoxic cells, and that suppressor cells were present dominantly in cancer patients. Furthermore, suppressor cells belonged to the distinct OKT8 positive fractions. Significant increase of T gamma cells in cancer patients was observed and the proportion of T gamma cells was positively correlated with advance of the disease. As for the tissue distribution, T gamma cells were present dominantly in the spleen and scantly in the lymph nodes, however, the increase of T gamma cells was observed in the lymph nodes with metastasis. The increase of IgG-Fc receptors on T cells and the induction of suppressor cells were observed simultaneously by co-culture with cancer sera.

Peripheral blood lymphocytes from gastric cancer patients and normal donors were divided into T, non T, Tr, and T non-r cell fractions. Suppressor cell activity of each fraction and surface antigen of T cell subsets were investigated. T and Tr cell fractions activated by concanavalin A (Con A) significantly depressed the lymphocyte proliferative responsiveness (LP) to phytohemagglutinin (PHA) of responder autologous lymphocytes, but non T and T non-r cell fractions didn't. LP response to PHA of responder autologous cells were depressed by Tr cell fraction from gastric cancer patients without Con A activation, but not from normal donors. The percentage of Tr cells in T cells increased from 8.9% to 18.2% in gastric cancer patients, and from 4.7% to 9.5% in normal donors when lymphocytes were activated by Con A for 24 hours. The percentages of Tr cells reacting with OKT3, 4, and 8 monoclonal antibodies were 72.5%, 29.0% and 43.4%, respectively. Therefore, Tr cell was relatively enriched by OKT8 cell. The percentage of Tr cells and suppressor cell activity increased when normal lymphocytes were incubated with sera from gastric cancer patients for 24 hours and suppression by T, Tr and T non-r cell fractions 23%, 8% and 5%, respectively. From these results it is suggested that Tr cells contain suppressor precursors which can be activated by Con A in vitro and matured suppressor cells which have been already activated in vivo, and that higher proportion of suppressor precursors is found in gastric cancer patients as compared with normal donors. Furthermore, it is indicated that cancer sera may contain factors which induce suppressor cell and induction of suppressor cell activity requires the interaction between Tr cell and T non-r cell.

FUT-175 is a new anti-complemental drug which strongly inhibits complement-mediated allergic reactions in animals. It was reported that FUT-175 does not affect both antibody formation and host defense to bacterial infection in mice. The present study was undertaken to examine the effects of FUT-175 on various immunological reactions in humans. FUT-175 dose-dependently decreased the antigen-induced anaphylactic histamine release from leukocytes of atopic patients. However, i.d. treatment of FUT-175 neither inhibited antigen- or compound 48/80-induced immediate type skin reactions in atopic patients nor antigen-induced early, late or delayed type skin reactions in Candida-sensitive patients. FUT-175 also did not inhibit the PPD-mediated delayed type skin reaction in healthy subjects. FUT-175 at a dose of 10(-4)M but not at 10(-8) to 10(-5)M significantly decreased the proliferation of human atopic peripheral blood lymphocytes (PBL) caused by mite antigen, concanavalin A or pokeweed mitogen. 51Cr release from human PBL was slightly enhanced by FUT-175 at a dose range of 10(-6) to 10(-4)M. FUT-175 did not change the number of SIg receptors or C3 receptors on human B cells. FUT-175 hardly affected the nitroblue tetrazolium reduction test and Escherichia coli-mediated chemotaxis in human neutrophils. These results strongly suggest that FUT-175 does not affect immunological functions and host defense in humans.