The receptor for C3b and C4b--complement receptor type 1 (CR1, CD35)--is present on a variety of cell types including erythrocytes, phagocytic cells, B lymphocytes and a small subpopulation of T lymphocytes. The function of the receptor varies according to the different cell types, but on T lymphocytes the function is as yet not known. The present study concerns the influence of polyclonal stimulation on CR1-expressing T lymphocytes. Incubation with PHA resulted in a dose-dependent increase in the number of CR1-positive T lymphocytes. The CR1-expression T lymphocytes were found in both the CD4- and the CD8-positive subpopulation, but a significant stimulatory increase was only found in the CD4-positive population. A significant increase in the number of CR1-expressing T lymphocytes was found when monocytes were present during stimulation, indicating an importance of monocytes and/or monocyte products. However, the increase was not regulated by arachidonic acid metabolites of the cyclo-oxygenase pathway as indomethacin failed to inhibit the increase. Neither did rIL-1 alpha, rIL-1 beta, rTNF alpha nor rIL-6 alter the number of CR1-expressing T lymphocytes. The results of this study indicate a role for CR1 on T lymphocytes in the regulation of the immune system.

T lymphocytes from 42 healthy blood donors were examined for expression of CR1 on the cell surface using a fluorescence-activated cell sorter. The fraction of CR1-positive T lymphocytes varied in the range from 1 to 8% (median 2.4%). The CR1-positive T lymphocytes constituted a homogeneous group of cells regarding both size and granulation; they seemed to be larger and more granulated than the average T lymphocytes. The CR1-expressing T lymphocytes were found both in the CD4- and in the CD8-positive subpopulations of T lymphocytes, and although the CD4-positive cells expressed CR1 with a slightly higher percentage than did the CD8-positive cells, this difference was not significant. The number of CR1-positive T lymphocytes did not correlate with the level of CR1 on erythrocytes. The presence of CR1 on a small T lymphocyte population suggests that CR1 on T lymphocytes might play a role in the immune regulation.

The present study was designed to examine the effect of physical exercise on human natural killer (NK) cells. Six healthy volunteers underwent two different acute physical exercise tests with an interval of at least 1 week: (1) 60min bicycle exercise at 80% of maximal oxygen uptake (VO2max) and (2) 60 min back‐muscle training at up to 29% of VO2max; blood samples were collected before and during the last few minutes of exercise, as well as 2 h and 24 h afterwards. The NK cell activity (lysis/fixed number of mononuclear cells) increased during bicycle exercise, dropped to a minimum 2 h later and returned to pre‐exercise levels within 24 h. Back‐muscle exercise did not significantly influence NK cell activity. Plasma levels of adrenaline, noradrenaline, and cortisol were elevated during bicycling, but not during back‐muscle exercise, indicating that exercise intensity is a determinant of NK cell activity. During bicycle exercise the NK cell subset (CD 16+ cells) of mononuclear cells increased significantly. Furthermore an improved interleukin 2 (IL‐2) boosting of the NK cell activity was found during work as compared to IFN‐α and indomethacin‐enhanced NK cell activity. These results indicate that NK cells with a high IL‐2 response capacity are recruited to the peripheral blood during exercise. The decreased NK cell activity demonstrated 2 h after work was probably not due to fluctuations in size of the NK cell pool, since the proportion of CD16+ cells was normal. The finding that indomethacin fully restored the suppressed NK cell activity in vitro and the demonstration of a twofold increase in monocyte (CD20+ cells) proportions 2 h after work, strongly indicate that prostaglandins released by monocytes during the heavy physical exercise are responsible for the down‐regulation of the NK cells.

Auranofin is a gold compound (triethylfosfine-gold) for peroral use which in clinical trials in patients with rheumatoid arthritis (RA) has been found superior to placebo (1-3) and comparable with parenterally injected gold salts (gold sodium thiomalate (GST) (Myocri-sin®) (3-6) or gold thioglucose (GT) (Sanocrysin®) and with orally administered D-penicillamine (D-pen) (7-10). Auranofin seems appropriate as an early alternative remission inducing drug (RID) in patients with active RA, since less severe side-effects have been reported. Although the pathophysiological action of auranofin is thought to be different from that of GST and GT it has been hypothesized that side-effects induced during GST and GT treatment may reappear during later gold therapy using auranofin. It is likewise an open question whether patients with active RA and a history of side-effects to or no effect of D-pen have an increased risk to develop auranofin side-effects. These questions have obvious clinical implications, since auranofin is a relevant and attractive drug for inducing remission in patients with active RA.

An experimental model was established in order to study the release of immune complexes (IC) bound by complement C3b receptors (CR1) on human erythrocytes (RBC). Soluble tetanus toxoid anti‐tetanus toxoid complexes were incubated with RBC in the presence of autologous serum at optimal conditions for binding. The RBC carrying complement‐opsonized complexes were incubated with appropriate serum reagents, and ii was shown that factor I was required for release of the complexes, which occurred without loss of CR1. Suramin was, irrespective of factor I, found to induce release of CR1‐bound IC in the absence of EDTA, whereas factor I‐mediated release was inhibited by soramin in the presence of EDTA. EDTA probably interfered through a charge‐dependent interaction. These observations are decisive for the interpretation of in vitro experiments involving these reagents. The combination of EDTA and suramin was found inappropriate for use in quantitative determination of in vivo CR1‐bound IC.

The microtiter plate ELISA using monoclonal antibody is a specific, sensitive and quantitative technique for measuring CR1 on human erythrocytes. The present investigations established that receptor occupancy by immune complexes did not affect the measurements. The monoclonal anti‐CR1 antibody To5 bound unimpeded to receptors that had reacted with an excess of complement‐opsonized tetanus toxoid anti‐tetanus toxoid complexes prepared at antigen: antibody ratios between 32:1 and 1:8. The CR1 levels on erythrocytes from 11 patients with systemic lupus erythematosus (SLE) were not increased (P > 0.30) after release of CR1‐bound immune complexes by incubation with factor I. Neither did the serum from these patients contain blocking anti‐CR1 activity (P > 0.10). Additionally, the number of antigenic CR1 sites in 10 normals and in the 11 patients with SLE was well correlated with the number of functional receptor sites as assessed by binding of soluble complexes (P < 0.001). These data establish that the true CR1 levels are determined using the microtiter plate ELISA for quantitation of CR1 in patients with diseases involving immune complexes and/or autoantibodies.

An enzyme-linked immunosorbent assay was developed for quantization of complement C3b receptors (C3bR) on human erythrocytes fixed in monolayer to microtiter plates. The disadvantages of macro test tube systems (large consumption of sample material and reagents, tedious washing procedures, cell loss and hemolysis) were avoided, and the fixed cells could be stored. In return a modest reduction in antigenicity induced by glutaraldehyde was inevitable. The calibration curve expressed a detection limit of about 10% and discrimination between levels of C3bR in the interval of about 10–120% of a standard erythrocyte with a high uptake of anti-C3b-receptor antibodies. The determinations of C3bR in normals as well as in patients varied within these limits, and showed a preponderance of low levels in the patients. The between-day coefficient of variation was 10.3%; the within-assay interplate and intraplate determinations respectively gave coefficients of variation of 9.7% and 6.2%. The method is suitable for further development and use for investigation of erythrocyte-bound immune complexes.

Anti‐ENA antibody determination by ELISA technique may offer a valuable diagnostic help in the discrimination of patients with mixed connective tissue disease (MCTD) from those with other chronic inflammatory connective tissue diseases. Determination of this antibody was performed in a prospective designed investigation among 101 blood donors, 154 patients with various non‐rheumatic internal medical diseases, and 229 patients with chronic inflammatory connective tissue diseases, including five patients with MCTD. A positive titre of anti‐ENA antibody was found in approximately 10% of blood donors and patients with various internal medical disorders. A highly positive anti‐ribonucleoprotein (RNP) titre was found in the patients with MCTD, but was also observed in patients with other chronic inflammatory connective tissue diseases, giving a predictive value of 56 % for MCTD. We conclude that highly positive anti‐RNP antibody values do not automatically indicate the diagnosis MCTD. Other diagnostic possibilities should still be considered.

Occurrence of autoantibodies against nuclear material was compared in groups of patients with rheumatoid arthritis (RA n = 22), systemic lupus erythematosus (SLE n = 24), osteoarthrosis (OA n = 25), and chronic schistosomiasis mansoni (CSM n = 28). Anti-ds DNA antibody was detected by an ammonium sulphate precipitation radioimmunoassay antibodies against extractable nuclear antigen (ENA) were detected and differentiated in RNAse-resistant and RNAse-sensitive components (Sm and RNP antigens) with an ELISA technique. IgG organ-non-specific and granulocyte-specific antinuclear antibodies (ANA) were detected by immunofluorescence technique with quantitative titration of positive reactions and determination of complement-fixing properties. The results in groups of patients with SLE, RA and OA were of confirmative nature and supported that the different methods detect different systems of autoantibodies and nuclear autoantigens. In CSM it was demonstrated that 23 of 28 cases had positive reactions to the RNAse-resistant part of ENA (the Sm-antigen), a significant difference from the three other groups of patients (P less than 0.001). The antibody was in all cases of IgM class, in seven cases also of IgA class. Antibodies against nuclear material in CSM are probably a consequence of heavy disturbance of the immune system in this chronic infection with great permanent antigen load. It is a matter of discussion, whether production of these antibodies is induced by nuclear material from the host or from the parasite.

Thirteen patients with stage I or II mycosis fungoides (MF) and 10 patients with large-plaque parapsoriasis en plaques (PEP) were examined for immunologic and cytogenetic disturbances. Total lymphocyte counts and immunoglobulin concentrations in the blood were normal. In vitro lymphocyte responses to polyclonal activators and various antigens in standard concentrations were normal. However, titration of phytohemagglutinin and concanavalin A (ConA) disclosed significantly lowered responses to suboptimal concentrations in the patient group, most pronounced in patients with MF II. ConA-induced leukocyte migration inhibitory factor (LIF) production, tested in an indirect leukocyte migration inhibitory assay, was low in the patient group. Furthermore spontaneous LIF production in vitro and small amounts of serum LIF were demonstrated in a few patients. The chromosomal banding pattern, sister chromatid exchange, and break frequency were within normal limits except for 3 translocations in the MF group. It is concluded that even in early-stage MF a pathologic function of blood lymphocytes can be demonstrated, when sensitive methods are applied. The findings might be important for monitoring disease activity and effect of treatment.