A B S T R A C T Lymphocytes that bind in vitro to

A B S T R A C T Sheep red blood cells can surround, in vitro, some human peripheral blood lymphocytes in a formation called a rosette. The number of rosetteforming cells (RFC) in 50 normal persons had a wide range (4-40%).The organs of 13 human fetuses (11-19 wk conceptional age) were examined for the presence of RFC. The thymus possessed the highest percentage of RFC, the maximum being 65% of total thymocytes in two 15-16 wk fetal specimens. Blood RFC were always present and their number slightly increased in the oldest fetuses. The bone-marrow showed 0-8% in the six fetuses studied. RFC were found in the spleen around the 13th wk and in the liver around the 17th wk of gestation. These observations lead to the hypothesis that human blood RFC may be chiefly thymic derived. Studies of patients with immunological disorders support this hypothesis: one patient with Nezelof syndrome had no blood RFC and four patients with Wiskott-Aldrich syndrome had a low number of blood RFC (1 and 1.5%). Patients with acquired hypogammaglobulinemia showed a normal percentage of RFC. With the fetal thymocytes, the percentage of inhibition with anti-i, serum increased with the fetal age to become complete in the oldest fetuses studied. Incubation of the oldest fetal thymocytes or the blood lymphocytes with anti-e serum or anti-ja serulmi completely inhibited the rosette formation. These results suggest that u-chain determinants are presenit on human fetal thymocytes and blood RFC. The significance of the presence of y-chain determinants on these cells is uniclear.Presented in part at the 84th annual meetiing of the Association

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The objective of this study was to analyze monokine production by peripheral blood mononuclear cells from patients with alcoholic cirrhosis. The capacity of peripheral blood mononuclear cells and purified monocytes from these patients to produce tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 was investigated. Spontaneous production of tumor necrosis factor alpha, interleukin 6 and interleukin 1 beta was similar in cirrhotic and healthy subjects, but serum levels of interleukin 6 (less than 2 U/ml vs. 9.5 +/- 3 U/ml) and tumor necrosis factor alpha (3.1 +/- 1.2 pg/ml vs. 12.0 +/- 1.2 pg/ml) were significantly higher in cirrhotic patients. However, peripheral blood mononuclear cells or purified monocytes from patients with alcoholic liver cirrhosis, stimulated in vitro with Escherichia coli lipopolysaccharide, displayed a marked increase of tumor necrosis factor alpha, interleukin 1 beta and interleukin 6 secretions compared with healthy controls. A striking feature of this overproduction was its reversibility as assessed by allowing cells to rest in vitro without lipopolysaccharide for 1 to 7 days before stimulation. In such conditions, tumor necrosis factor alpha and interleukin 6 secretions declined to levels present in healthy subjects in whom production remained stable, whereas interleukin 1 beta secretion markedly decreased in both groups to the point where no difference could be seen. This reversible oversecretion of cytokines after lipopolysaccharide stimulation, along with the lack of abnormality of spontaneous cytokine secretion, suggests that monocytes in these patients may have undergone an in vivo activation process analogous to a priming phenomenon. The in vitro activation with lipopolysaccharide may represent the correlate of in vivo endotoxemia observed during acute events such as sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

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Monoclonal antibodies specific to human T lymphocyte receptors are currently being used to define the biochemical structure of these proteins as well as of functionally distinct cell subsets. Since one of the antibodies (OKT3) recognizing the T3 (CD3) receptor mimics vital physiological processes involved in the activation of the immune system and has been successfully used as a therapeutical agent, we investigated one of the mechanisms underlying this antibody-receptor interaction. Our results show that after binding of OKT3, the complex (OKT3-T3) disappears rapidly from the cell surface. Using electron microscopy, we found that this down-regulation is due to the internalization of the complex. Parallel experiments performed on the T11 (CD2) and T4 (CD4)/AIDS retrovirus receptor indicate that the same mechanism applies for the down-regulation of those molecules. These data suggest that the T3, T11 and T4 receptors have a behavior comparable to other well characterized, hormonal and viral receptors; they provide information on the metabolization pathway of surface receptors and on the possible intracellular penetration of ligands like the HTLV-III/LAV agent in human T lymphocytes.

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