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Human T-cell subsets, defined by active E rosette formation, were examined for their ability to produce leucocyte migration inhibitory factor (LIF) in response to mitogen or specific antigen. It was determined that T cells enriched for active rosette-forming (A+) cells produced LIF in response to concanavalin A, whereas T cells depleted of active rosette-forming (A-) cells did not. Similarly, A+ cells from a tuberculin-sensitive donor produced LIF in response to tuberculin purified protein derivative, whereas A- cells from the same donor failed to produce the mediator. Thus, T-cell production of LIF in humans appears to be restricted to those T cells capable of active rosette formation. [ABSTRACT FROM AUTHOR]

B-cell 'activation" in cultures stimulated with pokeweed mitogen (PWM), Staphylococcus aureus strain Cowan I, or formaldehyde-fixed Salmonella paratyphi B (SPB) was evaluated by enumeration of cells secreting immunoglobulin (Ig) and by quantitation of Ig released into culture supernatants. A dissociation between these two values was found after day 6 in cultures activated with PWM or SPB, suggesting that Ig-secreting cells (ISC) are heterogeneous in terms of Ig secretion rate. Generation of ISC in cultures activated with PWM or SPB was partially inhibited by hydroxyurea, but Ig levels in culture supernatants were not affected. These results indicate that there are at least two subpopulations of ISC in stimulated peripheral blood lymphocyte cultures, one sensitive to and the other resistant to, hydroxyurea. The hydroxyurea-resistant subpopulation appeared to be more mature and to release almost all of the Ig detected in culture supernatants. Furthermore, time-course studies of ISC numbers and Ig levels showed that each ISC in SPB-stimulated cultures (but not in PWM-stimulated cultures) was more active in Ig synthesis and secretion after day 8 than before day 6. Indicating that after day 8 most of the ISC in cultures activated with SPB were hydroxyurea-resistant. These studies suggest that SPB is another useful polyclonal B-cell 'activator' for studies of human B-cell differentiation and function, and that SPB defines two distinct subsets of B cells. [ABSTRACT FROM AUTHOR]

We have studied two patients with common variable immunodeficiency (CVID), impaired cell-mediated immunity, and high percentages of monocytes in their peripheral blood. Removal of monocytes from cultures of peripheral blood mononuclear cells from both patients increased the in vitro responses to phytohaemagglutinin (PHA) and concanavalin A (Con A) but not to purified protein derivative (PPD), as measured by [³H]thymidine uptake. Similarly, supernatants of monocyte cultures from both patients, unlike supernatants of normal monocytes, suppressed the in vitro responses to PHA and Con A but enhanced the response to PPD by cultured mononuclear cells from the patients and form normal donors. Addition of unfractionated mononuclear cells from both patients to normal mononuclear cells suppressed both pokeweed mitogen (PWM) simulation and IgG production: this effect was abrogated by removal of monocytes from the patients' mononuclear cell populations. The effect of thymosin on both patients' mononuclear cells was assayed in vitro. Thymosin was ineffective in vitro with cells from the first patient; for the other patient, [³H]thymidine uptake by mononuclear cells stimulated with PPD increased, wheareas uptake by Con A-Stimulated cells decreased, as did the percentage of E rosette-forming cells, providing further evidence of heterogeneity of the CVID syndrome. The effects of thymosin were also dependent on monocytes. [ABSTRACT FROM AUTHOR]

This article focuses on the molecular theology and immunophilosophy. The present communication attempts to review the data and hypotheses regarding the aetiology and pathogenesis of adult rheumatoid arthritis (ARA) in a similar manner, and an admittedly controversial hypothesis differing from those currently accepted by most clinical immunologists is presented. When autologous or isologous IgG was injected into the joints of ARA patients, a clinical inflammatory reaction was produced, and this reaction was much more severe when autologous or Gm-matched isologous IgG was used than when Gm-mismatched IgG was used.

Human lymphocytes were cultured under different conditions to determine the effects of technical variations on the response to pokeweed mitogen (PWM) and Staphylococcus aureus as measured by (a) quantitation of immunoglobulins (Ig) in the culture supernatants and (b) enumeration of Ig-secreting cells (ISC) by a reverse plaque technique. The highest numbers of ISC were measured when the cells were cultivated in standing tubes, without glutamine supplementation during the culture, and at a concentration of 1 × 106 cells/ml. The highest Ig concentrations were measured under similar conditions, except that somewhat higher values were obtained with cells cultivated at 1 × 106/ml in 2 ml cultures with PWM stimulation and at 2.5 ×106/ml in 1 ml cultures with S. aureus stimulation. In time-course studies, peak ISC responses occurred on day 5 with each mitogen, whereas extracellular Ig levels kept rising until day 7, possibly owing to accumulation of secreted Ig. Measurements of the numbers of ISC and of secreted Ig levels in simultaneous cultures of lymphocytes from the same donors showed no correlation: however, co-stimulation of cultures with PWM and concanavalin A (to stimulate suppressor cells) depressed both Ig levels and ISC numbers. These results suggest heterogeneity in the plaque-forming cell population with respect to rate of Ig secretion, but indicate that these two techniques both reflect B-cell activation. They should not, however, be considered interchangeable, and the two probably should be used in conjunction for complete characterization of B-cell activation. [ABSTRACT FROM AUTHOR]

Discusses the significance of cellular immunology and cell-mediated immunity to certain autoantigens on autoimmune diseases. Description of autoantibodies; Prevalence of hypogammaglobulinaemia; Experiments on the discovery on the role of autoantibodies.

Carcinoembryonic antigen (CEA) activity was measured by radioimmunoassay in blood from cystic fibrosis (CF) homozygotes, heterozygote carriers of CF, normal healthy controls, and other patient controls with carcinomas involving gastrointestinal organs. All samples were also screened by electrofocusing for cystic fibrosis protein (CFP), a metabolic marker previously shown to be associated with the CF gene. Significantly increased levels of CEA activity were found in all CFP-positive groups; however, with one exception all patient controls with marked increases in CEA activity were CFP-negative. Immunodiffusion of perchloric acid extracts of CEA-like material from heterozygote carrier blood indicated that the CEA-like material, which was elevated in homozygotes and heterozygotes for CF, showed only partial identity with two separate CEA preparations obtained from colon carcinomas and was not identical to either A, B, or O (H) blood group substances. Tlus glycoprotein material did, however, react with three different anti-CEA antisera. Our finding of an abnormally increased glycoprotoin in cystic fibrosis, taken together with previous reports demonstrating abnormalities in the carbohydrate portion of glycoproteins found in various exocrine secretions in CF, further suggests that the primary defect in this disease is manifested partly as a defect in glycoprotein metabolism. This defect may result from an abnormality in one or more of the glycosyltransferases, possibly caused by a more primary defect in polyamine metabolism. [ABSTRACT FROM AUTHOR]

Studies of a monoclonal IgA(λ) protein with both cryo- and pyro-precipitability show that it belongs to the IgA2 subclass and is positive for the A2m (2) allo-typic marker. Like other cryoglobulins, this protein also has an unblocked light chain, and its heavy chain belongs to the VHI subgroup. The first 22 N-terminal amino acids of the λ chain of this protein showed less than 65% homology with those of other human λ chains but showed 86% identity with that of an amyloid fibril protein reported by others. The α chain of this protein appears to have more glutamic acid or glutamine, or both, and less isoleucine residues than other human α chains. [ABSTRACT FROM AUTHOR]

Salmonella paratyphi B (S. paratyphi B) has been previously characterized as a human T-independent polyclonal B cell activator. To define further the nature of the bacterial structure responsible for these properties, we studied the effects of autoclaving and enzyme treatment of S. paratyphi B on its stimulatory capacity. We found that both autoclaving and papain treatment decreased the ability oF S. paratyphi B to induce B cell activation, while trypsin treatment did not affect this capacity. Neither type of treatment affected the binding of S. paratyphi B to lymphocytes, suggesting that binding and B cell stimulation are mediated by different structures. The observation that B cell stimulation was significantly reduced by papain treatment led us to attempt to purify membrane proteins so that we could investigate whether they shared the stimulating capacity of S. paratyphi B, A water-insoluble, 43–45,000 mol. wt. protein, rich in aspartic acid, glutamine, glycine, alanine and leucine, similar in mol. wt. and physicochemical properties to the porins of other gram negative bacteria, was isolated and designated as outer membrane protein (OMP). This protein was equally efficient to S. paratyphi B in inducing T-independent B cell activation. By performing time-course studies of [3H]-thymidine incorporation we observed a burst of mitogenic activity after stimulation of PBL or purified B cells with both S. paratyphi B and OMP peaking at 48–96 hr of culture (compared to 96–120 hr for the PWM proliferation peak), and with a magnitude of roughly 10% of that observed after PWM stimulation. Given the fact that the proportion of B lymphocytes in PBL is 4–12%, it appears likely that the proliferation burst seen with S. paratyphi B and OMP corresponds to a mitogenic effect mainly restricted to the B cell population. [ABSTRACT FROM AUTHOR]

The two-stage leukocyte migration agarose test (indirect LMAT), shown to be a sensitive in vitro assay for cell-mediated immunity, was used to study Kveim reactivity in vitro in patients with sarcoidosis. No Kveim-induced inhibition of leukocyte migration in agarose or Kveim-induced lymphocyte transformation in vitro was found in 23 patients with sarcoidosis, suggesting that the Kveim reaction is not an expression of cell-mediated immunity. [ABSTRACT FROM AUTHOR]

Endometriosis occurs in 4-17% of females of reproductive age and is often associated with primary and secondary infertility (Lachlan. 1972; Ranney, 1980). However, the factors governing its aetiology are not clear. Genetic, hormonal, enzymatic and immunological phenomena have been postulated (Weed & Arguembourg., 1980). Complement component C3 is found lining the epithelial cells of endometrial glands in patients with endometriosis. indicating possible formation of immune complexes (Weed & Arguembourg. 1980) A reduction in the number of T lymphocytes and an increase in the amount of immunogiobulin in endometrial tissue have been reported in 56 patients with endometriosis (Startseva, 1980). The presence of autoantibodies to endometrium in these patients, however, has not been established. Moreover, endometriosis is sometimes associated with anovulation (Soules (et al., 1976) and inadequate corpus luteum function (Grant. 1966; Hargrove & Abraham, 1980). Since patients with anovulation and ovarian disorders may have ovarian antibodies in their circulation (Fialkow, 1966; Mathur et al., 1980a,b; Coulam & Ryan, 1979), it is possible that patients with endometriosis may have ovarian and endometrial autoimmunity. Also, since endomelriosis is a disease involving the reproductive tract, a study of cervical and vaginal secretions would seem relevant, [n the present study, sera and secretions from patients with endometriosis were tested for the presence of autoantibodies to ovary and endometrium. [ABSTRACT FROM AUTHOR]

Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000-25,000 which had all the activities of unseparated TS. [ABSTRACT FROM AUTHOR]

The possible influence of sex steroid hormones on circulating IgE levels in general and IgE anti- Candida antibodies in particular was studied by quantification of plasma levels of progesterone, estradiol and IgE (total and anti-Candida-specific) in females during the follicular and luteal phases of the menstrual cycle, and during pregnancy. IgE levels during the follicular and luteal phases were not significantly different, although the mean values for the luteal phase were slightly lower. This trend was apparent in daily samples from two normal females during one menstrual cycle. During pregnancy, when the levels of circulating sex steroids were high, IgE levels were only slightly higher than in the follicular and luteal phases. In men and in gonadal dysgenetics, circulating progesterone levels were similar to those of women during the follicular phase (i.e., lower than in the luteal phase or in pregnancy), but the IgE levels were not different. The apparently low levels of IgE during the luteal phase may therefore be due to physiological factors other than fluctuations in the sex steroid hormones. From the present studies, it is apparent that sex steroid hormones have little or no effect on humoral IgE levels, in marked contrast to previously described correlations for other immunogiobulins, especially anti-Candida antibodies. [ABSTRACT FROM AUTHOR]

Antibodies to native human collagen were detected by passive haemagglutination in the serum of sixteen of thirty-six subjects with selective IgA deficiency (44.4%), compared to 2-5% of control subjects. The sixteen subjects with anti-collagen antibodies included four asymptomatic subjects, five with recurrent infections, four with ataxia telangiectasia, and one each with lymphoma, asthma, and rheumatoid arthritis. There was no statistically significant correlation in individual subjects between the presence of anti-collagen antibodies and antibodies to human IgG, IgA, IgM and ruminant proteins. [ABSTRACT FROM AUTHOR]

The metabolism of radio-iodinated IgG was studied in seven patients with IgG deficiency (<600 mg/100 ml). The group comprised two patients with primary hypogamma-globulinaemia, one with primary hypogamma-globulinaemia and nodular lymphoid hyperplasia, and one each with chronic lymphatic leukaemia (CLL), γG multiple myeloma, renal homotransplantation and the nephrotic syndrome. All patients had markedly reduced plasma and total body pools of normal IgG with normal distribution (intravascular and extravascular pools). An increase in the initial urinary excretion of free isotope in one patient was attributed to a degree of protein denaturation. Compared to the normal range of 20-60 mg/kg/day for IgG synthesis, the patients with primary deficiency and the patient with CLL all had markedly reduced synthesis of normal IgG (2, 5, 4 and 7 mg/kg/day respectively). These patients also had a prolonged or normal plasma T½ and a normal or decreased fractional turnover rate (FTR). The patients with deficiency of normal JgG secondary to multiple myeloma, renal homotransplant or nephrotic syndrome all had an IgG synthesis rate at the lower limit of the normal range with values of 19, 21 and 19 mg/kg/day respectively. They had increased catabolism with a short plasma T½ and increased FTR. An assessment of the factors controlling the metabolism of normal IgG is important in the individual patient as regards the management of their recurrent infections with therapeutic human γ-globulin. [ABSTRACT FROM AUTHOR]

Metabolic turnover studies were performed with radio-iodinated IgG in twelve patients with a serum IgG level greater than 1600 mg/100 ml (six with monoclonal gammopathy and six with a polyclonal increase in IgG associated with liver disease). The six patients with an IgG monoclonal protein comprised four multiple myeloma, one benign monoclonal gammopathy and one biclonal gammopathy presenting as Waldenström's macroglobulinaemia. The six patients with liver disease comprised two patients with cirrhosis, two with infective hepatitis and two with chronic active hepatitis. The injected IgG was either autologous normal IgG (five cases), autologous monoclonal IgG (five cases), homologous normal IgG (one case) or therapeutic intravenous HGG (two cases). The plasma volume was increased in six patients; the plasma IgG pool in nine; and the total body IgG pool in seven. The plasma T½ was normal in one patient with monoclonal and one patient with polyclonal gammopathy but shortened in the other ten studies with mean values of 11.3 and 11.0 days in monoclonal and polyclonal gammopathy respectively. The fractional turnover rate was normal in two studies in polyclonal gammopathy and increased in the other ten with mean values of 13.6% per day in both groups of patients. The IgG synthesis rate was significantly increased in all studies except for a reduced synthesis of normal IgG in one patient with multiple myeloma. The mean synthesis rates in monoclonal and polyclonal gammopathy were respectively 6.7 and 4.1 times the mean synthesis rate in normal controls. The pattern of increased synthesis and increased catabolism in such patients confirms published reports in some diseases and demonstrates a similar pattern in chronic active hepatitis. The findings are consistent with the `concentration-catabolism' effect. [ABSTRACT FROM AUTHOR]

The article focuses on the cost and benefits of biomedical research. Data on the cost benefits from basic and applied biomedical research indicates that benefits have exceeded the cost by 20-fold. Hence, cutbacks in funds for biomedical research represent fiscal irresponsibility. Everyone is aware about the funding of biomedical research in the past five years by the U.S. National Science Foundation, and reported allocations by the administration for the next fiscal year, have remained at more or less a constant level.