Thymus-derived rosette-forming cells.
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Biomedical subjects
Publications and source records attributed to J Wybran.
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Lymphocytes that bind in vitro to sheep erythrocytes in a rosette formation are thymus-derived. A modified technique that does not detect the total number of rosette-forming cells (RFC) was used to study normal subjects and various disease states. Of 100 healthy subjects, 95 had more than 15% RFC (mean 28.4+/-6.5%). We studied 104 patients with solid tumors, who were classified according to clinical status and stage of therapy. Of 19 newly diagnosed patients, 13 had less than 15% RFC. Of 44 untreated patients undergoing relapse, 32 had less than 15% RFC. In both categories, patients with metastases had fewer RFC than patients with localized disease. 11 patients were studied 2 wk after cessation of therapy; four of them showed less than 15% RFC. Only one of 30 patients in remission had less than 15% RFC. In seven patients followed for various periods of time, the numbers of RFC correlated generally with clinical status. 11 patients with chronic lymphatic leukemia had very low percentages of RFC. 21 of 21 patients with symptoms of viral upper respiratory diseases had less than 15% RFC. RFC returned to normal values between 5 days and 7 wk after disappearance of clinical symptoms. 20 patients with bacterial infections had normal numbers of RFC. Of 25 patients with miscellaneous nonimmunologically related diseases, two had low numbers of RFC. It appears that the percentage of RFC may be valuable in evaluating not only immunological defenses but also the status of patients with solid tumors, lymphomas, viral diseases and, perhaps, bacterial infections.
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-mu 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-gamma serum of anti-mu serum completely inhibited the rosette formation. These results suggest that mu-chain determinants are present on human fetal thymocytes and blood RFC. The significance of the presence of gamma-chain determinants on these cells is unclear.
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A fluorometric assay is described for the detection of red blood cell antibodies. The assay reveals as little as 600 molecules of bound, fluoresceinated rabbit anti-human IgG antibodies per erythrocyte. Eleven patients with possible autoimmune erythrocyte disorder and negative direct antiglobulin test were studied by the fluorometric assay. The outcome of the fluorometric assay was compared with that of the human allogeneic rosette test. Results obtained by the two methods were in complete agreement. Five of the patients were shown to possess unexpectedly high levels of erythrocyte-bound IgG in spite of a negative, direct antiglobulin test. These findings and the validity of the fluorometric assay are discussed.
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In an open study inosiplex, a new synthetic immunomodulatory drug, was given to 15 patients with rheumatoid arthritis (RA) 3 g daily until clinical improvement occurred and then tapered. Nine of 15 patients experienced clinical benefit evidenced by a reduction of morning stiffness, fewer tender joints, decreased proximal interphalangeal joint circumference, and decreased sedimentation rate and fibrinogen level. Three patients responded rapidly to inosiplex (in two weeks) and a clear cut improvement was noticed within 1 month by all the responders. Two patients showed an exacerbation of the disease. No toxic drug effect was noticed. Although the mode of action of inosiplex in RA appears unclear, its rapidly of action and high rate of response should encourage further study of its use in the treatment of RA.
This review summarizes some of the recent observations regarding the active T-rosette assay. This test, performed under suboptimal technical conditions, identifies a subpopulation of T lymphocytes with high-avidity receptors for sheep red blood cells. They are Ia-positive but appear to lack an Fc receptor. They can be either OKT4-positive or OKT8-positive. Isolated active T-rosette populations are capable of recognizing and killing allogeneic cells and they also modulate B-cell immunoglobulin production. They are directly correlated in vivo with specific cutaneous reactivity to an antigen. More interestingly, the percentage of active rosettes specifically increases in vitro after one hour of incubation with soluble or cellular antigens. This test fully correlates with the lymphocyte stimulation test. In the case of human mixed lymphocyte culture, the increase in active T rosettes is due to antigenic differences in the HLA D-DR region. The neoformation of active T rosettes is due to the early release of a rosetting factor. Drugs which are able to modulate T-cell functions, such as thymosin, transfer factor, isoprinosine and NPT-15392, also increase the percentage of active T rosettes. Therefore, the newly formed active T rosettes appear to be an early marker for lymphocyte activation.