Search

We tested the possibility that lymphocytes and serum obtained directly from a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) induce infection in rats. Inbred Fischer F344 immunosuppressed rats were inoculated intravenously with 10x10(6) peripheral blood mononuclear cells (PBMC; 3 rats) and serum (3 rats) obtained from a HAM/TSP patient, who was seropositive and polymerase chain reaction (PCR)-positive for the HTLV-I proviral genome. Antibodies to HTLV-I appeared in the rat sera 2 months later; rat peripheral blood lymphocytes, spleen, salivary gland, and spinal cord were found to contain the proviral genome. Control rats inoculated with normal donor PBMC and serum tested negative for the HTLV-I antibodies and for the HTLV-I proviral genome by PCR. The positive control F344 rats inoculated with 5x10(6) cells of a SLB-1 HTLV-I cell line were found to be infected after 2 months. This study demonstrates for the first time that HTLV-I can be transmitted not only by human cellular components but also by human cell-free sera in a rat model.

Soluble interleukin 2 receptor (SIL-2R) and interleukin 1-B (IL-1B) levels in peripheral blood were assayed by enzyme-linked immunoabsorbent method in 25 patients with Behçet's disease and in 20 healthy controls. Eighteen patients suffered from active Behçet's disease and 6 patients had severe disease manifestations. SIL-2R levels were followed for a period of 16 months and were correlated with disease activity. In all the patients with Behçet's disease the levels of SIL-2R and IL-1B were significantly higher than their control, 958 +/- 712 vs. 404 +/- 119 u/ml (P0.001) for SIL-2R and 639 +/- 741 vs. 59 +/- 53 pg/ml (P0.001) for IL-1B. No correlation was found between disease activity and severity and the levels of SIL-2R and IL-1B. It is suggested that levels of SIL-2R and IL-1B are elevated in patients with Behçet's disease but do not serve as disease activity markers.

Background Inflammatory reactions have an important part in atherosclerosis. Smooth muscle cells, endothelial cells, monocytes, and T lymphocytes are actively involved. The purpose of this study was to assess whether T lymphocytes are activated in patients with stable angina pectoris who are candidates for a percutaneous transluminal coronary angioplasty (PTCA) and the influence of PTCA on this process. Methods and Results Twenty-four patients participated in the study. All were 40- to 60-year-old men, and all but one underwent successful PTCA. Blood samples were taken 1 day before PTCA and 1 week, 1 month, and 2 months after. Two groups of patients were detected: group A, 11 patients who had high levels of soluble interleukin-2 receptor (sIL-2R) before PTCA that decreased toward normal during the follow-up period in most of them; and group B, 13 patients who did not have elevated sIL-2R levels before PTCA and in whom sIL-2R levels did not change after the procedure. Group C consisted of 15 healthy men whose sIL-2R levels were in the normal range (control subjects). Conclusions (1) T lymphocytes are activated in stable angina patients. (2) The level of sIL-2R can be a reliable laboratory marker for follow-up of patients after PTCA, especially those with high sIL-2R levels before the procedure.

Corticosteroids are known to affect the number and function of circulating lymphocytes in humans. The effect of 2 years administration of inhaled budesonide (200 micrograms/day) on the number and function of B and T lymphocytes and T cell subsets was evaluated in 16 young children with severe asthma. The number of T and B cells and T suppressor/cytotoxic cells (CD8 T cell) and T helper/inducer cells (CD4 T cell) before therapy was found to be comparable to the number of cells observed in the healthy control group. Two years administration of inhaled budesonide did not significantly alter the percentage and absolute number of all these cells. The functional activity of T lymphocytes was evaluated by the "local xenogeneic graft versus host reaction" (GVHR). A positive (normal) GVHR was observed in only 5 of the 16 children (31%) in the budesonide group before therapy, compared to 15 of 16 children (94%) in the healthy control group. During the 2 years treatment with inhaled budesonide, the percentage of patients having positive GVHR increased from 31% before therapy to 69% and 77% after 1 and 2 years of therapy (P = 0.05 and 0.02), respectively. The data observed in this study indicate that 2 years administration of inhaled budesonide did not alter the number of B and T lymphocytes and T cell subsets. However, it was associated with improvement in the GVHR function of T cells.

Seventy patients with Duke's C adenocarcinoma scheduled to undergo surgery were divided into two groups, those who received no peri-operative transfusion (Group I, 26 patients) and those who received an average of 2.1 units of packed red blood cells per person peri-operatively (Group II, 44 patients). Immunological parameters were tested 1 week before and 1 and 5 weeks after surgery in order to determine the influence of the transfusion of these parameters. Comparison of the mean values obtained before operation with those obtained one week post-operatively revealed a significant change in the number of B cells (P = 0.014), with a decrease in Group I and an increase in Group II, which was seen to persist for the mean values obtained 5 weeks after surgery. The higher rates of recurrence and the lower rates of survival reported in patients who received transfusion may be related to an as yet unidentified role of B cells or a subpopulation in the immune system, manifested in the suppression of activity of those components responsible for destroying micrometastases. In relation to the site of the tumor no definite conclusions can yet be drawn as to the prognostic importance of our findings concerning the immunological parameters.

A 33-year-old male of proven fertility suffered six attacks of malaria while resident in an African country. For this he received anti-malarial drugs. Semen analysis performed after the fourth attack, and repeated during the following 2 years after his return to Israel, revealed severe oligozoospermia, necrozoospermia and occasionally even azoospermia. Immunological examination of the patient revealed an inverse ratio of T-cell subsets and mast cell degranulation in response to palludrin. Twenty-five months after the last attack of malaria a significant improvement was found in semen quality and there was an increase in the ratio of T-helper to T-suppressor cytotoxic cells. These observations indicate that although malaria and its treatment may affect spermatogenesis, recovery may be expected eventually.

In 10 patients with mycosis fungoides (MF) who were in clinical remission following local treatment with nitrogen mustard, cell-mediated immunity was investigated by means of tests for lymphocytes, forming rosettes in the peripheral blood, and the graft-vs-host reaction as well as intradermal skin tests. The effect of thymic humoral factor (THF) on T lymphocytes with impaired immunecompetence was also investigated. The results provided evidence of various kinds of damage to the immunologic system in most of the patients. Of the 10 patients, 4 had low percentages of T cells. Eight of the 10 had a graft-vs.-host reaction which was weak or negative, and in 4 of these, the administration of THF to the lymphocytes induced an improvement in immunoreactivity. These results together with other recently reported data indicate that the determination of cell-mediated immunity in patients with MF may be of prognostic importance. Those patients whose T lymphocytes respond to treatment with THF are probably the best candidates for immunotherapy.

Lymphoid cells obtained from a mediastinal mass and bone marrow as well as peripheral blood of a patient with poorly differentiated diffuse malignant lymphoma were found to have both E and complement receptors. Addition of the bone marrow lymphoblasts to normal human T-lymphocytes induced a suppression of normal T functional activity as measured by a local xenogeneic graft versus host reaction. Incubation of the same cells with thymic humoral factor (THF), a thymic hormone, reversed their functional activity from suppression to help. Control studies with normal T-suppressor lymphocytes also showed a reversal of function to helper activity upon incubation with THF. In studies of normal T-lymphocytes with monoclonal antibodies, incubation with THF induced no change in phenotype in either theophylline-sensitive (suppressor) cells or theophylline-resistant (helper) cells. The ability of THF to modulate helper and suppressor activities suggests that this or similar agents may provide a useful means of therapy for disorders of immunoregulation.

The local graft-versus-host reaction (GVHR) and the spontaneous rosette-forming cell (RFC) test were used to test the functional activity of lymphocytes in blood obtained from twenty normal donors and thirty patients with malignant tumours. The lymphocytes of all twenty control donors gave a positive GVHR and had normal RFC values. In twenty-two of the thirty patients with malignancies the GVHR was negative; of these, only five had low RFC values. In the remaining eight patients the GVHR was positive and RFC values were normal. It is concluded that the local GVHR constitutes a sensitive test for measurement of the functional activity of lymphocytes, while the RFC test can only be used as a quantitative test.

Peripheral blood lymphocytes from a patient with T cell chronic lymphocytic leukemia were examined by a combination of cell markers (E and M rosettes, and surface Ig), the graft-vs.-host reaction, thymic humoral factor (THF) and scanning electron microscopy. It was not possible, at first, to determine by conventional methods whether the leukemic cells were of the B or T type, but the THF and graft-vs.-host reaction showed that T cell precursors were present. These cells were incompetent immature T cells that underwent maturation following treatment with THF. Three months later, the T cell nature of the disease was clearly demonstrated by the E rosette technique, although at this time the cells were no longer influenced by THF.

Lymphocytes were obtained from a lymph node biopsy from a patient with chronic lymphocytic leukemia in whom B and T lymphocytes were present in equal percentages in the peripheral blood. The lymphocytes were examined for rosette formation with mouse and sheep erythrocytes in order to determine whether the leukemic process was of the B or T cell type.

Nineteen children with mumps meningitis were investigated. Peripheral blood T cell subset function and number were tested during the acute phase of meningitis and again when the children recovered. No significant difference in the total number of T cells, or T helper: suppressor lymphocyte cell ratio was found in the children with mumps meningitis as compared with the controls. However, a significant increase in the number of T suppressor/cytotoxic cells in the peripheral blood of children with mumps meningitis in the acute phase was found. This increase in the T suppressor subset was still present even after the children recovered from the disease. Two children who showed deafness had the highest increases in the T suppressor/cytotoxic lymphocyte subset. Functional analysis of T suppressor cell activity demonstrated a significant suppressive activity of lymphocytes obtained during the acute phase of the disease. However, after recovery the suppressive activity found was not significant (P greater than or equal to 0.1).

The local graft-vs-host reaction (GVHR) test was used to assess the cellular immune competence of lymphocytes obtained from 29 patients with malignant tumors of the gastrointestinal tract before and after removal of the tumor. Prior to removal most patients showed impairment of cellular immune competence; 10 to 14 days after surgery there was an improvement in a considerable number of patients. However, when tested four months later, the GVHR was again negative in some patients. The possible factors leading to deficiency in cellular immune competence and the value of the local GVHR test in the long-term follow-up of patients who have had malignant disease are discussed.

The number of circulating T-lymphocytes and their functional activity were studied in a group of 14 uremic patients prior to and after 6 to 9 months of treatment with continuous ambulatory peritoneal dialysis (CAPD). Low absolute T cell counts were found on initial examination in five of eight patients tested. There was no change in T cell counts after CAPD. The functional activity of T cells was tested by the local xenogeneic graft vs. host reaction (GVHR). Of the 14 patients tested with this technique, 10 initially showed impaired T cell functional activity. After CAPD a clear improvement in functional activity of the T cells was found in 4 of 10 patients with impaired GVHR. In three of these four patients, an inhibitory factor that had been present in the serum disappeared after CAPD.

Two patients with subacute sclerosing panencephalitis (SSPE) showed impairment of cell-mediated immunity, as indicated by a low T cell number, decreased intracellular cyclic AMP levels of peripheral blood lymphocytes, negative graft-vs.-host reaction in vivo, negative skin reactions to common antigens and, in one of the patients, abnormal reactions in migration inhibition factor tests. Since some of the impaired T cell functions in one of the patients were reconstituted in vitro by the administration of thymus humoral factor (THF), a thymic hormone shown in an earlier study to regulate maturation of T lymphocytes in in vitro and in vivo animal models, a course of THF administration was given to both patients in this study. In vitro and in vivo assays, which reflect T cell competence, were performed before and after a daily schedule of THF administration that lasted for 10 days in one patient and 21 days in the other. The results of this preliminary trial suggested that THF was capable of reconstituting the impaired T cell functions in both patients after a short term of treatment. These preliminary results should encourage additional long-term therapeutic trials with THF in SSPE patients with impaired cell-mediated immunity.

Reports in the literature have suggested possible impairment of immunocompetence in operating theater personnel. In a group of 18 physician anesthesiologists the following were determined: hemoglobin concentration; white blood cell count; numbers of T, B, and natural killer (NK) lymphocytes; number of T-active cells; and numbers of T-helper/inducer (Th) and T-suppressor/cytotoxic (Ts) cells; and the Th/Ts ratio. Function of T lymphocytes was evaluated using the local xenogeneic graft-versus-host reaction and spontaneous suppressor or helper activity of T cells. The same parameters were determined in a group of 18 age- and sex-matched healthy controls. It was found that no matter what their age or how long they have been engaged in anesthetic practice, anesthetists show no immunosuppression as evidenced by these parameters.

THF, a partially purified Thymic Hormone, was shown to restore the impaired cell mediated immunity (CMI) and reduce the visceral complications in 4 children with acute leukemia and generalized varicella. Twelve children with acute lymphocytic leukemia (ALL) or lymphoma were treated with THF for generalized varicella infection associated with impaired CMI. CMI parameters were studied before, during and post THF therapy. It was found to increase significantly (two- to ten-fold) the number of peripheral blood lymphocytes, E-rosettes, response to ConA, PHA and intracellular cAMP in 11 children. The number of lymphocytes and E-rosettes increased from 700 to 6000 and from 250 to 5500 per Cu.mm respectively. All children recovered from the varicella infection, including two with severe bilateral pneumonitis, and all of them developed antibodies to V-Z virus. Similar results of the above mentioned CMI parameters were obtained in 6 additional immunosuppressed children with ALL & lymphoma, 4 of whom had severe pneumonitis. THF restored positive GVHR and skin tests in 8 out of 10 and 4 out of 9 children studied respectively. These observations suggest that THF may restore the impaired CMI in children with ALL & lymphoma and may be valuable as supportive therapy of severe viral infections.