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Publications and source records attributed to Z Toossi.
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It is not clear whether the accessory function of monocytes from subjects with human immunodeficiency virus (HIV)-related diseases such as acquired immunodeficiency syndrome (AIDS) and persistent generalized lymphadenopathy (PGL) is intact. In this study, the accessory function of monocytes from healthy subjects (n = 9) and subjects with AIDS (n = 4) and PGL (n = 5) was assessed by adding graded numbers of monocytes to lymphocytes stimulated with either tetanus toxoid or phytohemagglutinin. By nonparametric analysis, it was determined that a significantly greater number of monocytes was required for half-maximal responses of lymphocytes from subjects with PGL (for tetanus toxid but not phytohemagglutinin) and from those with AIDS, compared with healthy subjects. To address whether this observed difference was a result of a defect in accessory function of monocytes or a result of altered responsiveness of lymphocytes, a mixing experiment was performed between monocytes and lymphocytes obtained from a patient with PGL but without symptoms and an HLA-D-matched healthy sib. Dysfunction of both monocytes and lymphocytes was evident. Thus, this report provides data that monocytes in HIV infection are defective in accessory function for lymphocyte responses to soluble stimuli. We speculate that such dysfunction of monocytes may contribute to the progressive disturbance of the immune response that occurs during HIV infection.
Nine patients with the acquired immunodeficiency syndrome (AIDS) were administered four doses of pooled transfer factor obtained from the lymphocytes of three healthy controls and three homosexuals with stable lymphadenopathy and serum antibody to the human immunodeficiency virus. Before receiving transfer factor, all patients exhibited anergy to skin test antigens. After four weeks of transfer factor therapy, six of seven patients tested had at least one skin test response. Lymphocyte blastogenic responses to phytohemagglutinin rose from a stimulation index of 6.77 +/- 1.31 before treatment to 19.77 +/- 6.24 after four weeks of transfer factor therapy. Smaller but significant increases were also seen in blastogenic responses to antigens. Improvements in immune responses diminished after administration of transfer factor was halted. Thus, administration of transfer factor to patients with AIDS resulted in partial immune reconstitution. Further studies are indicated to examine the clinical efficacy of this immune response modifier in the treatment of AIDS.
U937, a human macrophage-like cell line, spontaneously produces a factor which inhibited blastogenic responses of human blood T lymphocytes stimulated with tuberculin-purified protein derivative (PPD) or phytohemagglutinin (PHA). We investigated the mechanism of suppressor action of the U937 factor. The U937 suppressor factor inhibited interleukin 2 (IL 2) production by human blood T lymphocytes stimulated with PPD or PHA. IL 1 did not overcome the inhibitory action of the U937 factor on PPD-induced IL 2 production by human blood T lymphocytes. The U937 factor also inhibited the production of IL 2 by a human leukemic cell line, JURKAT, stimulated with PHA. The U937 suppressor factor interfered with the expression of Tac antigen (IL 2 receptor) on PPD- or PHA-stimulated blood T lymphocytes. The inhibitory activity of the U937 factor on Tac expression was not affected by the addition of IL 2 or a crude lymphokine-containing T cell supernatant. Tac expression was more sensitive than IL 2 production to inhibition by U937-conditioned medium. The U937 suppressor factor was precipitable by 33 to 67% saturated ammonium sulfate and was inactivated at pH 2 or pH 11. Sephacryl S-200 Gel filtration analysis of U937 culture supernatants revealed that the inhibitory activities for blastogenesis, IL 2 production, and Tac expression co-purified in fractions with an apparent m.w. between 67,000 and 130,000. These data indicate that U937 spontaneously produces a macromolecular suppressive factor with major locus of action on the production of IL 2 and the expression of the IL 2 receptor.
The clinical distinction between bacterial colonization of the tracheobronchial tree and nosocomial pneumonia is difficult, especially in intubated patients. We studied 51 intubated, intensive care unit patients prospectively by serial examinations of tracheal aspirates for elastin fibers, graded Gram's stains, and quantitative bacterial cultures in conjunction with clinical and radiologic observations in an attempt to develop criteria for the early detection of pulmonary infection. Patients with infection had new or progressive pulmonary infiltrates plus 1 of the following: positive blood culture results, radiographic evidence of cavitation, or histologic evidence of pneumonia, or 2 or more of the following: new fever, new leukocytosis, or grossly purulent tracheal aspirates. Twenty-one patients developed infection, 22 remained colonized, and 8 had an uncertain status. Infiltrates developed in 34 patients (21 infected, 8 colonized, 5 uncertain status). Gram-negative bacilli were most commonly isolated and were more frequent in infected patients (81 versus 47%, p less than 0.05); Pseudomonas aeruginosa and Serratia marcescens were most often associated with infection. No differences were observed between infected and colonized patients in demographic features, smoking history, underlying disease, previous antibiotic therapy, days in hospital before intubation, preexisting pneumonia upon intubation, or highest temperature or leukocyte count during course. By univariate analysis, infected patients had a longer duration of intubation (p less than 0.05), higher Gram's stain grading for neutrophils (p less than 0.05) or bacteria (p less than 0.005), higher bacterial colony counts (p less than 0.05), and more frequent detection of elastin fibers in tracheal aspirates (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Patients with newly diagnosed, pulmonary tuberculosis had a tuberculin-specific defect in IL-2 production. Mean PPD-induced IL-2 activity was 81.2% lower in patients as compared with healthy tuberculin reactors. PPD-induced expression of T cell IL-2 receptors was 5.9 times less in peripheral blood mononuclear cells of patients with tuberculosis as compared with healthy tuberculin reactors. Furthermore, purified IL-2 failed to correct PPD-induced blastogenesis in patients. Suppression by adherent cells was operative in one group of patients; adherent cell depletion increased their T cell production of IL-2 7.2-fold. A second group of patients with low IL-2 production did not have suppressor adherent cells and were clinically distinct, with more extensive disease on chest x ray. The basis for low IL-2 production in such individuals is unknown. Disordered regulation of IL-2 metabolism may be a key feature in the depressed cellular immune response of tuberculosis.
To examine the role of antihemophilic factor (factor VIII) preparations in the pathogenesis of subclinical immunodeficiency in hemophilia, we tested the in vitro effects of these products on immune function. Both lyophilized antihemophilic factor (LAHF) and cryoprecipitates inhibited lymphocyte proliferation in a dose-dependent fashion. Further studies indicated that LAHF interfered with an early event in proliferation and also that prolonged incubation of human lymphocytes with LAHF resulted in an irreversible inhibition of lymphocyte proliferation without detectable cytotoxic effects. LAHF also inhibited the production of interleukin-2 (IL-2) by human lymphocytes and by Jurkat tumor cells, suggesting that inhibition of IL-2 production was not mediated through effects on interleukin-1. Gel filtration of LAHF revealed two peaks of inhibitory activity; one with mol wt greater than 2 X 10(6) comigrated with factor VIII coagulant activity and antigen, whereas another with mol wt approximately 6 X 10(5) was devoid of factor VIII activity and antigen. Further study will ascertain whether administration of factor VIII-containing preparations contributes to the subclinical immunodeficiency seen in patients with hemophilia or serves as a cofactor in the development of clinical immunodeficiency after exposure to the retrovirus human T-lymphotropic virus type III.
Simulated positive blood cultures with 84 known stock strains of streptococci were used to comparatively evaluate the direct identification of these organisms by fluorescein-tagged antibody staining (immunofluorescence [IF]) and latex agglutination (LA). IF was not evaluated for Lancefield group D strains (a total of 81 strains tested) and had 89% sensitivity and 91% specificity. IF was least sensitive for the identification of Lancefield group F, in which three of seven strains showed no fluorescence with the group F reagent. Since LA was more convenient and revealed comparable sensitivities and specificities on 84 simulated cultures, we tested this procedure using an additional 29 fresh positive clinical blood cultures, for a total of 113 cultures tested by this technique. Of 11 Streptococcus pneumoniae strains, 9 reacted with the LA group C reagent, a problem not observed with IF. However, all these strains were identified by a rapid modified bile solubility test. Of the 12 Streptococcus faecalis strains, 4 were falsely negative with the group D reagent, but all were correctly identified by a rapid litmus milk reduction test. Of 12 group A strains, 1 was not detected. Of all 113 strains tested by LA, eliminating S. faecalis and S. pneumoniae, the sensitivity and specificity were 97 and 98%, respectively. LA was simple and reliable in the rapid identification of streptococci from blood cultures and appeared to be preferable to IF. When LA is used, the group D reagent should not be used, and all samples reacting with the group C reagent should be tested by a modified rapid bile solubility test to exclude S. pneumoniae.
We observed a human urine-derived protein complex (IL-2-IN) which competitively inhibits interleukin-2 (IL-2) dependent murine lymphocyte proliferation. Measurements of urinary IL-2-IN have been used to stratify the immune response of patients to bacteria in the bladder. Partial characterization of IL-2-IN indicates that it is a heat-stable, 75 kDa complex comprised of interleukin-2 bound to another protein(s). Although the IL-2-IN complex is stable in physiologic buffers, the complex can be disrupted using acidic or low-ionic strength buffers, thereby liberating IL-2. IL-2-IN activity is susceptible to bacterial and endogenous urinary proteolysis. The IL-2 bound in the IL-2-IN complex cannot be detected using a double monoclonal antibody radioimmunoassay for IL-2. Unlike other IL-2 binding proteins, the IL-2 binding protein of the IL-2-IN complex is not a soluble interleukin-2 receptor. A modification of the bioassay for interleukin-2 activity is the method of choice for the detection and quantification of urinary IL-2-IN.