[Beguez-Cesar, or Chediak-Higashi, disease: study of a case in pseudo-lymphoma phase (author's transl)].
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Biomedical subjects
Publications and source records attributed to M Kreisler.
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Normal human peripheral blood lymphocytes were shown to activate complement in normal human serum (NHS). This activation led to C3 fixation on the cell membrane, which in turn was visualized by fluorescence. The reaction occurred in the absence of detectable amounts of antibodies, since an agammaglobulinemic patient's serum also supported complement activation, and the results were unaltered by absorption of normal human serum. Trypsin treatment of lymphocytes to remove possible complement activators bound to the cell membrane, did not have any effect on the complement activation by lymphocytes. Complement membrane fluorescence was abolished in the presence of EDTA or ethyleneglycolbis(aminoethylether) tetraacetate (EGTA) supplemented by Mg++ions indicating that the classical pathway of complement activation was involved in the reaction. Experiments performed with T and B-purified populations showed that the phenomenon was confined to the B cell fraction. Complement deposition did not diminish the number of EAC rosettes, and viability remained unchanged after exposure of lymphocytes to normal human serum.
A simple technique for isolating human peripheral B and T cells is described. This method is based on the different mobility of cells in a discontinuous density gradient of Percoll. A population with a mean of 72.8% of surface stable Ig (B cells) is found in the top layer (fraction I) whereas T cells with less than 3% of Ig are distributed in the two lower layers (fractions II and III). B cells obtained by this method were highly viable and reacted strongly with anti-DRw specific sera, whereas T cells did not respond. The clear-cut difference between positive and negative reactions makes this technique very suitable for DRw typing. The proliferative response to PHA is decreased in fractions I and III while greatly increased in fraction II. The different mitogenic responses in the two fractions containing T cells probably represent two functionally distinct T cell subsets. Cells from all fractions are less activated than unseparated cells when Con A and PWM are used as mitogen. The technique is very rapid, avoids the interaction of cells with their specific receptors and gives both T and B cells in one step, all advantages over other methods commonly used.
Normal human lymphoid cells from peripheral blood, spleen, tonsils and thymus were examined for their ability to mediate three different cytotoxic effector cell functions: antibody-dependent cellular cytotoxicity (ADCC); lectin-induced cellular cytotoxicity (LICC) and natural killer activity (NK), against 51Cr labelled erythroid and tumor target cells. We found a hierarchy of cytotoxic activities in the different lymphoid tissues. Peripheral blood and spleen cells were able to mediate LICC, ADCC and NK activities. Tonsil cells showed a natural segregation of the different cytotoxic functions: NK and ADCC activity against tumor target cells were absent, whereas LICC activity was fully present. With respect to ADCC activity against erythroid targets, tonsil cells showed low, but significant, cytotoxicity. Thymus cells had no detectable ADCC, NK and LICC activities. Correlation in the different lymphoid tissues between cytotoxic activities and cell surface marker studies revealed: (a) that the presence of E-SRBC rosette forming cells was not always associated with the detection of LICC activity, as is the case with the thymus; (b) that, in the absence of detectable Eox-7S rosette forming cells (thymus and tonsils), NK and ADCC activities against tumor cells were always absent, but LICC was observed (tonsils), indicating that the presence of this Fc(7S) receptor bearing cells is strongly associated with the expression of NK and ADCC but not with LICC.
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We have used a cytoplasmic enzyme system in the study of the in vitro cytotoxic activity of human peripheral blood leucocytes against isolated liver cells in patients with chronic liver diseases. Lymphocytes from primary biliary cirrhosis and chronic active liver disease patients were shown to have an in vitro capacity to induce a cytolitic effect on isolated hepatocytes, as demonstrated by the enhanced release of lactate dehydrogenase (LDH), a cytoplasmic marker enzyme. No significant LDH release was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis. Our results corroborate, in a different assay system, by a simple, reproducible and different method, that lymphocyte-mediated liver cell damage "in vitro" occurs in both primary biliary cirrhosis and chronic active liver disease.
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Mitochondria isolated from rat livers were used as a source of antigens capable of producing in vitro activation of lymphocytes that had previously been sensitized in vivo with the same antigen. Such lymphocytes were shown to have an injurious effect on target mitochondria, as was demonstrated by a new biochemical approach based on the study of the inhibition by these cells of mitochondrial respiratory control. A somewhat milder injurious capacity was also observed in normal and sensitized lymphocytes activated in vitro with the mitogen PHA. The lateration of the respiratory control of mitochondria by lymphocytes correlated with an increase in DNA synthesis in these cells.
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