We examined the sensitivity of lymphocytes from different age groups to inhibition by prostaglandin E2. Phytohemagglutinin-stimulated cultures of peripheral blood mononuclear cells from 12 healthy subjects over the age of 70 were much more sensitive to inhibition by exogenously added prostaglandin E2 than were cells from 17 young controls (ID50 congruent to 10 nM for the subjects over 70 vs. greater than 3 micronM for the young controls). The more senstivie lymphocytes from a subject over 70 were to prostaglandin E2, the lower was his or her response to phytohemagglutinin (r = 0.75, P less than 0.01). The mean responses to phytohemagglutinin of the peripheral blood mononuclear cells from the subjects over 70 were significantly depressed compared to the young controls. Addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures resulted in an increase in [3H]thymidine incorporation of 140 +/- 16% in the cells of the subjects over 70 vs. a 36 +/- 3% increase in the young controls (mean +/- SEM, P less than 0.001). The mean phytohemagglutinin response of the subjects over 70 was 40% of the control response without indomethacin. With addition of indomethacin the response of subjects over 70 rose to 72% of control. Thus, increased sinsitivity to prostaglandin E2 appears to be responsible in part for the depressed mitogen response of peripheral blood mononuclear cells from healthy subjects over 70.

Adult↗

PubMed1979

Suppressor cell function in sarcoidosis.

We investigated the role of suppressor cells in the depressed cellular immunity of patients with sarcoidosis. The mean response in 16 patients with active sarcoidosis to three concentrations of phytohemagglutinin was significantly (P less than 0.01) less than control values. Passage of the cells over glass wool resulted in a 116% increase in response to phytohemagglutinin in patients and a 39% decrease in control subjects. Addition of indomethacin to phytohemagglutinin cultures increased the response of cells in patients with sarcoidosis by 192% +/- 32% versus a 112% +/- 18%-increase for control subjects (mean +/- SEM, P less than 0.05). Patients had an increased percentage of monocytes in peripheral blood mononuclear cell preparations, and the percent monocytes correlated with the percent increase in phytohemagglutinin response after glass wool passage (r = 0.62, P less than 0.05). Thus, several factors contribute to the depressed phytohemagglutinin response in sarcoidosis patients: an increased suppression by the prostaglandin-producing suppressor cell, an increased percentage of monocytes, and an as yet undefined factor.

Adult↗

PubMed1978

Antilymphocyte antibodies in systemic lupus erythematosus patients and their relatives: reactivity with nonhuman lymphocytes.

Explore the source record for details and available documents.

Absorption↗

PubMed1978

Prostaglandin E inhibition of mitogen stimulation in patients with multiple sclerosis.

Kirbey et al have reported that leukocyte function from patients with multiple sclerosis is not suppressed by PGE2, as are normal leukocytes. We examined the ability of PGE2 (0.01-0.5 microgram/ml) to suppress Phytohemagglutinin induced 3H-thymidine incorporation in peripheral blood lymphocytes from multiple sclerosis patients and normals. There was no difference in sensitivity between the two groups. There was also no difference in activity of the prostaglandin producing suppressor cell between the multiple sclerosis patients and controls.

Humans↗

PubMed1978

Effect of indomethacin in vivo on humoral and cellular immunity in humans.

We studied the effect of indomethacin on intradermal skin testing and antibody responses in humans. Since we and others have shown that prostaglandins are suppressor cell mediators, it was probable that in vivo inhibition of prostaglandin synthesis might enhance the humoral and/or cellular immune response. Administration of indomethacin (Indocin) in a dosage of 100 mg/day to 15 normal men and women resulted in a significantly increased antibody titer to A-Victoria (P less than 0.025) as compared with age- and sex-matched controls. There was no difference in titer to A-New Jersey. Since 90% of the subjects had antibody titers to A-Victoria before inoculation, whereas none had detectable titers to A-New Jersey, we interpret this data as suggesting that indomethacin enhances the secondary but not the primary humoral immune response. Indomethacin administration did not alter the intradermal skin test responses.

Adult↗

PubMed1978

Prostaglandin suppression of mitogen-stimulated lymphocytes in vitro. Changes with mitogen dose and preincubation.

In this study we further characterize the properties of the prostaglandin-producing suppressor cell. Overnight preincubation of peripheral blood mononuclear cells results in an increased response of the cells to phytohemagglutinin or Concanavalin A compared to the response of fresh cells. This increase in mitogen response with preincubation was similar in magnitude to the increase in mitogen response of fresh cells after the addition of indomethacin. The two manipulations were not additive; that is, after preincubation, indomethacin caused much less enhancement of mitogen stimulation of peripheral blood mononuclear cells (100 +/- 12% increase before preincubation vs. 12 +/- 6% after preincubation; mean+/-SEM, P < 0.001). Preincubated cells also lose sensitivity to inhibition by exogenous prostaglandin E(2). It requires the addition of 100- to > 1,000-fold more exogenous PGE(2) to produce comparable inhibition of phytohemagglutinin-stimulated preincubated cells than is required for inhibition of phytohemagglutinin-stimulated fresh cells. The enhancing effect of indomethacin increases with decreasing doses of phytohemagglutinin. Indomethacin causes a 1,059+/-134% increase in [(3)H]thymidine incorporation at the lowest dose of phytohemagglutinin (0.2 mug/ml), and a 4+/-3% increase at the highest dose (20 mug/ml). This increase in response to indomethacin with a lower dose of phytohemagglutinin is due to increased sensitivity to inhibition by PGE(2) at lower mitogen doses. The prostaglandin-producing suppressor cell assay and the short-lived suppressor cell assay measure over-lapping phenomena. The increased suppressive effect of the prostaglandin-producing suppressor at suboptimal mitogen dose must be taken into account in the interpretation of any study where the response to a range of mitogen doses is studied.

Adult↗

PubMed1978

Isolated trigeminal sensory neuropathy: early manifestation of mixed connective tissue disease.

A young woman with mixed connective tissue disease (MCTD) had an isolated trigeminal sensory neuropathy as an early manifestation of the disease. Raynaud phenomenon occurred almost synchronously with the onset of trigeminal neuropathy and was followed by myositis, diffuse hand swelling, synovitis, and increased ribonucleoprotein antibody. Mixed connective tissue disease has overlapping features of systemic lupus erythematosus, scleroderma, and polymyositis, and is differentiated from them by high-titer antibody to ribonucleoprotein.

Adult↗

PubMed1978

Epidemiology of anti-lymphocyte antibodies in systemic lupus erythematosus.

Lymphocytotoxic antibodies (LCTA) occur in 80% of SLE patients and 40% to 60% of their asymptomatic relatives. They occur equally in consanguineous and nonconsanguineous relatives, are more common with close proband contact, and vary directly with LCTA activity in the proband. LCTA are also increased in laboratory personnel handling SLE blood. Anti-RNA antibodies are found in SLE patients and consanguineous relatives. Both antibodies are primarily IgM in relatives but are IgM and IgG in SLE patients.

Autoantibodies↗

PubMed1978

Partial reversal of the cellular immune defect in common variable immunodeficiency with indomethacin.

We administered indomethacin (25 mg q.i.d.) to two patients with common variable immunodeficiency and measured the effect on their depressed cellular immune responses. The in vitro response of both patients' lymphocytes to phytohemagglutinin increased during indomethacin administration. Both patients were anergic to skin testing before treatment and responded to two of four skin tests during treatment with indomethacin. Thus indomethacin administration in vivo appears to enhance the cellular immune respone, paralleling its previously described effects in vitro.

Adolescent↗

PubMed1977

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

Small amounts of PGE inhibit mitogen-induced [3H]thymidine incorporation in human peripheral lymphocytes. The 50% inhibitory concentration is approximately 10(-7) M, and this is reduced to approximately 10(-8) M when endogenous PGE production is blocked. PGE inhibits PHA- and Con A-stimulated cultures much better than PWM cultures, suggesting a differential effect of PGE on T-cell vs. B-cell function. In vitro blockade of PG synthesis results in approximately 50% increase in [3H]thymidine incorporation in PHA cultures. PGE is produced endogenously in PHA cultures by glass adherent suppressor cells.

Cyclooxygenase Inhibitors↗

PubMed1977

Prostaglandin-producing suppressor cells in Hodgkin's disease.

We examined the role of a prostaglandin-producing suppressor cell in the hyporesponsiveness to phytohemagglutinin seen in Hodgkin's disease. Addition of indomethacin to phytohemagglutinin cultures of lymphocytes from six patients with Hodgkin's disease resulted in an increase of 182 +/- 60 per cent in 3H-thymidine incorporation versus a 44 +/- 18% increase in 29 controls (mean +/- S.D., P less than 0.001). Without indomethacin the mean response of the lymphocytes in Hodgkin's disease was 48% of that of control. With indomethacin it was 94% of the control value. Phytohemagglutinin cultures of Hodgkin-disease lymphocytes produced approximately fourfold more prostaglandin E2 after 48 hours than did normal lymphocytes (P less than 0.02). Removal of glass-adherent cells markedly decreased the enhancement seen with indomethacin; it reduced prostaglandin E2 production by more than 80% and eliminated the differences in response to phytohemagglutinin between Hodgkin-disease and normal lymphocytes. Thus, a glass-adherent, prostaglandin-producing suppressor cell is responsible for the hyporesponsiveness to phytohemagglutinin seen with Hodgkin-disease lymphocytes.

Adult↗

PubMed1977

Antilymphocyte antibodies in systemic lupus erythematosus: familial clustering of lymphocyte antigens.

Cold reactive lymphocytotoxic sera from patients with systemic lupus erythematosus and their relatives were found to react with lymphocyte antigens that cluster in normal families. These antigens do not correlate with HLA-A or -B antigens in families, suggesting that they are not related to Ir genes. Further work is indicated to determine whether these antigens are controlled by several genes or involve viral products on the cell surface.

Antigens↗

PubMed1977

Detection of antilymphocyte antibodies in patients with systemic lupus erythematosus by indirect immunofluorescence on acetone-fixed lymphocytes.

Antilymphocyte antibodies in normal and SLE sera were found to react with lymphocytes fixed in acetone at -30 degrees C. for 10 minutes. At a dilution of 1:40, 3.7 per cent of normal and 90.9 per cent of SLE sera were positive with the use of indirect immunofluorescence with a pepsin-digested, FITC-labeled anti-Fab serum. The reaction was independent of temperature between 4 degrees and 37 degrees C. Three patterns of staining were seen in the lymphocyte surface: reticular, ring, and globular. The ring pattern appeared to correlate with IgM, and the reticular and globular patterns with IgG antilymphocyte antibodies. Absorption with lymphocytes, insolubilized extracts of rat liver and kidney, and human brain revealed that antilymphocyte and ANA activity could be independently removed. Variation in reactivity with cells from different normal donors was similar to that seen with the microcytotoxicity test. Acetone-fixed lymphocytes appear to be a much more sensitive target than viable cells in suspencion in IIF tests for antilymphocyte antibodies. The IIF test with fixed cells also appears slightly more sensitive than cytotoxicity testing and has the advantage of allowing storage of target cells.

Antibodies, Antinuclear↗