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J J Oger

Publications and source records attributed to J J Oger.

At least 37 records · Page 2Linked to original sources
PubMed1989

Regulation of in vitro PWM-induced IgG secretion in humans.

PWM-induced differentiation of human PBMC into immunoglobulin (Ig) secreting cells is a widely used model of in vivo IgG secretion. We examined the relationship between the amount of IgG secreted in PBMC cultures obtained from individuals who consistently secrete either very high (HR) or very low amounts (LR) of IgG and various in vitro immune function assays. The PBMC obtained from LR contained a higher ratio of cells expressing the T-suppressor/inducer to T-helper/inducer phenotype. The autologous mixed lymphocyte response was lower and the amount of in vivo radiation sensitive suppression was higher in the LR than in the HR. LR E- cells secreted less IgG than the HR E- cells when both were mixed with heterologous HR E+ cells. Monocyte depletion reduced IgG secretion in both LR and HR. These results suggest that each of the subsets Ts, Th (Thi, Tsi), and B lymphocytes are involved in the regulation of PWM-induced Ig secretion and that the functions of each of these subsets differ in HR and LR individuals.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

The lesion of multiple sclerosis: imaging of acute and chronic stages.

Increased blood-brain barrier (BBB) permeability, important in the pathogenesis of MS, may be demonstrated as lesion enhancement with high-volume delayed CT (HVDCT). We studied 40 MS patients with history, neurologic examination, HVDCT, and MRI. In addition, 7 of the patients with enhancing CT lesions were followed with serial MRI for up to 3 years and 7 months. In 3 of these patients we repeated the HVDCT. Patients with enhancing lesions on CT were younger, had shorter duration of disease, and had more frequent clinical relapses than did patients without enhancement. More than half (56%) of the enhancing CT lesions were in the deep white matter, 23% were periventricular, and 21% were at the gray/white matter junction. Half the CT enhancing lesions, when followed by serial MRI, showed significant changes in lesion size. Although the majority (59%) of these lesions faded, some remained actively changing (25%) or became confluent with adjacent lesions (16%). In 48% of the MRI examinations that showed activity, some lesions were increasing in size while others were simultaneously decreasing in size. This study confirms that MS is a dynamic process in which recurrent episodes of BBB disruption and inflammation play a major role. Recurrent episodes of inflammation may well be a prelude to the largely irreversible changes of demyelination and gliosis.

Acute Disease↗
PubMed1988

MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT.

We compared the diagnostic capabilities of MRI to CT, evoked potentials (EP), and CSF oligoclonal banding analysis in a prospective evaluation of 200 patients with suspected multiple sclerosis (MS). MRI was the best method for demonstrating dissemination in space. An abnormal appropriate EP in monosymptomatic disease was usually supported by MRI and CSF analysis as being predictive of MS as a clinical diagnosis. A normal appropriate EP study was not satisfactory because MRI and CSF analysis often did not support a diagnosis of non-MS. When there is agreement between three of these paraclinical studies, the diagnosis of MS is probably unequivocal. For use in research studies, laboratory-supported definite MS (LSDMS) could be diagnosed in 85 patients of the total 200 (42.5%), in 19/38 (50%) of optic neuritis (ON) patients, and in 24/52 (46%) of chronic progressive myelopathy (CPM) patients. MRI was 100% successful in identifying patients who qualified for LSDMS in the ON and CPM groups. In a short follow-up (less than 1 year), 19/200 (10%) went on to develop clinically definite MS (CDMS), and MRI predicted that diagnosis in 18/19 (95%). Only long-term follow-up will show how well these studies and the category of LSDMS predict the development of CDMS. The clinical diagnosis of MS (CDMS), even though only 95% accurate, must remain the gold standard.

Adolescent↗
PubMed1984

Low T8 antigen density on lymphocytes in active multiple sclerosis.

The median fluorescence intensity of peripheral blood T8+ (T-suppressor/cytotoxic) cells in patients with active (relapsing or progressive) or stable multiple sclerosis (MS) and in control subjects was determined with a fluorescence-activated cell sorter using an indirect immunofluorescence assay. Median fluorescence intensity was significantly lower in patients with active MS than in controls. No differences in median fluorescence intensity were found between patients with stable MS and controls. Analysis of T8+ cells that had been modulated in vitro with OKT8 indicated that the resultant reduction in the median T8 antigen density per cell resulted in fewer T8+ cells being enumerated when the fluorescence-activated cell sorter was used than when a fluorescence microscope was used. Reduced median T8 antigen density on cells as found in active MS may contribute to the apparent underrepresentation of circulating T-suppressor cells in such patients and may be associated with reduced suppressor cell function.

Adult↗
PubMed1984

Multiple sclerosis: relation of in vitro IgG secretion to T suppressor cell number and function.

The proportion of MS patients whose pokeweed mitogen-stimulated mononuclear cells (MNCs) secreted greater than 1,000 ng/ml IgG per 10(6) cells (ie, "high responders") was increased compared with controls. The suppressor effect mediated by a constant number of T8+ cells from high responders, both MS and control, on IgG secretion by standard T helper (T4+) plus B-cell cultures was significantly lower than that for the same number of T8+ cells from "low responders." The proportion of T8+ cells within MNCs from MS patients did not correlate with levels of IgG secretion. Our results indicate that high levels of IgG secretion by MNCs, an occurrence overrepresented in the MS population, is significantly influenced by functional properties of T suppressor cells.

Adolescent↗
PubMed1984

T cell regulation of polyclonally induced immunoglobulin secretion in humans.

We measured the pokeweed mitogen (PWM)-induced secretion of IgG by the unfractionated mononuclear cells (MNC) of young adult donors, and correlated the results with the functional activity of cell suspensions enriched for T helper (T4+) and T suppressor/cytotoxic (T8+) cells. The distribution of IgG levels secreted by MNC differs from a Gaussian curve, implying that the group is composed of distinct heterogeneous populations. When donors were compared who were judged to be very low responders or very high responders on the basis of IgG secretion levels by MNC (less than 700 ng/ml or greater than 2500 ng/ml), no differences were found in the capacity of T4+-enriched cells to support PWM-driven IgG secretion by a common B cell pool. In contrast, the addition of 0.2 X 10(5) T8+ cells from these low responders to PWM-stimulated cultures of 0.5 X 10(5) T4+ cells plus 0.5 X 10(5) B cells resulted in significantly less IgG secretion (389 +/- 121 ng/ml) than did the addition of the same number of T8+ cells from the high responders (2241 +/- 548 ng/ml, p less than 0.01). Normalized percent suppression by T8+ cells was higher in low responders than in high responders (77.0 +/- 9.9% vs 33.0 +/- 8.5%, p less than 0.01). Both high and low responders markedly suppressed IgG secretion when 0.5 X 10(5) T8+ cells were added. No correlation was found either between proportion of T3+, T8+, T4+, or M1+ cells within the MNC population and levels of IgG secretion by MNC or between T8+ numbers and levels of suppression induced by a constant number of T8+-enriched cells. Our data indicate that differences in the functional activity of T8+ cells, rather than quantitative differences, account for the wide range of PWM-induced IgG secretion by MNC.

Adult↗
PubMed1983

Modulation of T lymphocyte differentiation antigens: influence of aging.

In vitro modulation of human T lymphocyte surface differentiation antigens T3, T8, and T4, by their respective monoclonal antibodies, was studied as a function of donor age. Kinetic studies performed on lymphocytes from young adults indicated that modulation is dependent on concentration of antibody used and duration of culture. OKT3 modulates T3 rapidly (maximum at less than 24 hr) and relatively completely (79% at the highest concentration of antibody used). By 48 hr, regeneration of the T3 antigen is apparent. T8 modulation by OKT8 is slower (continued modulation at 48 hr) and less complete than is T3 modulation by OKT3. OKT4 does not modulate the T4 antigen. In elderly individuals modulation of T3 by OKT3 is preserved whereas modulation of T8 by OKT8 is significantly reduced (24 +/- 8% at 48 hr vs 53 +/- 4% for young controls). These observations document further age-related changes in properties of human T suppressor cells.

Adult↗
PubMed1983

Mechanisms responsible for reduced in vitro immunoglobulin secretion in aged humans.

Age-related changes in the processes involved in T cell dependent polyclonal B cell activation in man were studied by comparing immunoglobulin (Ig) produced in autologous T:B (E+:E-) cell cultures of young and old donor pairs with Ig produced in crossover cultures. Each young and old donor was classified as a responder or a non-responder based on Ig levels in autologous pokeweed mitogen-activated T:B cultures. The data indicate that: (1) T suppressor influences are a major determinant of non-response in the young; (2) T cells of nonresponder old donors can support high levels of Ig secretion by young donors' B cells; (3) low response to pokeweed mitogen stimulation in the elderly may reflect either direct refractoriness of B cells to T cell dependent stimulation, heightened B cell sensitivity to suppressor signals, or a combination of the two.

Adult↗
PubMed1982

Influence of azathioprine (imuran) on in vitro immune function in multiple sclerosis.

In vitro immune function was assessed in patients with multiple sclerosis (MS) who were receiving Imuran therapy, in untreated MS patients, and in controls. In untreated stable MS patients, concanavalin A (Con A)-driven mitogenic reactivity (T effector function) and Con A-induced suppressor activity were modestly reduced compared to controls; pokeweed mitogen-induced immunoglobulin G (IgG) secretion was increased. Untreated patients with active MS demonstrated high levels of IgG secretion and marked decreases in suppressor activity. In Imuran-treated patients, Con A mitogenic responses and suppressor activity were comparable to those observed in untreated stable patients, and IgG secretion was reduced. The results in the treated patients likely reflect a direct effect of Imuran on B cell function rather than an indirect effect mediated via suppressor cells.

Adolescent↗
PubMed1982

HLA profiles in multiple sclerosis suggest two forms of disease and the existence of protective haplotypes.

261 multiple sclerosis (MS) patients were HLA-A and -B typed and 94 were HLA-D typed. The results were compared to those of controls typed for HLA-A; HLA-B (356) and HLA-D (113). We confirm and extend earlier findings (Oger et al. 1980b) that some phenotypes could modulate the expression of the MS susceptibility gene linked to B7-DR2: DR3 was found together with DR2 in 12/94 MS and only 3/113 controls and could be marker for an "augmentor" gene. In contrast, B35 and DR1 as well as B12 and DR7 could be markers of protector genes. We compared typing results of patients subgrouped on clinical features. 61 patients with progressive evolution showed increased A1, A1-B8, B8-DR3 and A1-B8-DR3 when compared to 200 patients with remitting evolution. When compared to controls both groups showed increased B7 but only the remitting group showed increased DR2. 71 patients with "benign MS" showed increased B7-DR2 and A3-B7-DR2. 54 patients with "severe disease" showed increased DR3 and A1-B8-DR3 when compared to controls. Both groups showed increased B7 (49.2% and 44.4% versus 25.5% for controls). 120 patients treated greater than 5 years with azathioprine were divided into "no progression" and "progression" while treated. Both groups showed increased B7 when compared to controls. DR2 was increased only in the "no progression" group. B8-DR3 and A1-B8-DR3 were found increased in the "progression" group only. We conclude that two forms of MS exist with different HLA profiles.

Adolescent↗
PubMed1982

Modulation of T-lymphocyte differentiation antigens: potential relevance for multiple sclerosis.

Effects of the anti-T-cell monoclonal antibodies OKT3, OKT5, and OKT8 on T-cell surface properties and cell functions were evaluated. Incubation of mononuclear cells isolated from peripheral blood for 48 hr with each monoclonal antibody in the absence of complement resulted in modulation of their respective surface antigens; i.e., the number of cells detected by immunofluorescence as positive for the T3, T5, and T8 surface antigens was reduced. T3, T5, and T8 antigens modulated independently. A radiolabeled second antibody technique confirmed modulation by OKT3 and OKT8 and indicated that T-cell differentiation antigens can regenerate in culture. Incubation of mononuclear cells with OKT3 increased the number of sheep erythrocyte-binding lymphocytes (E+-rosetting cells) and markedly increased the number of avidly E+-rosetting cells. Incubation with OKT8 reduced the number of E+- and of avidly E+-rosetting cells. OKT3 induced both mitogenic reactivity and suppressor cell activity; cells modulated by OKT8 exhibited reduced mitogenic reactivity and reduced suppressor cell function. The decreases in total T cells, in avid T cells, in suppressor cell number, and in suppressor cell function that follow modulation by OKT8 mimic changes observed in multiple sclerosis patients.

Adult↗
PubMed1982

Competition for immune complexes by red cells in human blood.

Antigen:antibody complexes, prepared with 125I-bovine serum albumin and guinea or rabbit antibody, were added to serum and blood cells from normal individuals and binding studied. When antigen:antibody were pre-incubated with serum in varying proportions for 30 min at 37 degrees C and then mixed with washed unseparated cells, binding increased to a maximum (70% of added complexes) and then decreased as serum to antigen:antibody proportions were increased. Separation of cells revealed that following maximal binding to unfractionated cells, complexes were predominantly associated with red blood cells (RBC), even though complexes bound less per cell to RBC than to white blood cells following addition of complexes to separated cells. Binding to RBC was reduced by zymosan treatment of serum and abolished by heat inactivation or substitution of non-primate RBC (known not to possess C3b receptors) for human RBC, indicating that binding to human RBC was via C3b receptors. When antigen:antibody were incubated at 37 degrees C directly with serum and unfractionated blood cells, maximal binding occurred after 2-4 minutes and declined thereafter. Identical kinetics were observed when purified RBC were substituted for whole blood cells. When diluted or hypocomplementemic (systemic lupus erythematosus) serum was substituted for neat serum, maximal binding was delayed and sustained. Our findings suggest that RBC in human blood can compete with other cell types for immune complexes at that stage during the sequence of reactions between complexes and complement when complexes are able to bind to C3b receptors.

Animals↗
PubMed1982

Restoration of normal interactions between immune complexes and systemic lupus erythematosus blood cells by normal serum.

Blood cells from patients with systemic lupus erythematosus (SLE) and from healthy control subjects were studied for their ability to bind exogenous immune complexes. Cells were mixed with experimental complexes (prepared from 125I-radiolabeled bovine serum albumin [BSA] and guinea pig antiserum to BSA) after incubation of the complexes with autologous serum in variable proportions. Unfractionated blood cells from SLE patients bound fewer added complexes (mean +/- SD = 39.8% +/- 12.9%) than cells from normal controls (mean +/- SD = 63.6% +/- 9.5%) (p less than 0.001); as much as 128-fold (mean = 23-fold) higher (p less than 0.01) proportions of serum to complex were required to optimize the lower binding. When SLE blood cells were mixed with complexes preincubated with normal sera instead of autologous SLE sera, SLE cells bound increased amounts of added complexes, and binding was optimal at the same lower proportions of serum to complex as for normal cells. When normal cells were mixed with complexes preincubated with compatible SLE sera in place of endogenous normal sera, binding to normal cells decreased to SLE levels, and the same higher proportions of serum to complex were required to optimize the lower binding as for the SLE cells. Similar results were obtained when binding to purified mononuclear cell preparations from SLE patients and controls was studied. When comparative studies were performed at high complex-to-cell ratios with complexes prepared using normal sera, SLE cells bound fewer complexes per cell than normal cells. These results indicate that although abnormalities in SLE cells are demonstrable, the major factor accounting for aberrant interaction between immune complexes and SLE cells resides in alterations in SLE sera.

Adolescent↗
PubMed1982

Kinetics of interaction of immune complexes with complement receptors on human blood cells: modification of complexes during interaction with red cells.

Antigen-antibody complexes, composed of 125I-BSA and guinea-pig or rabbit antibody, were incubated at 37 degrees C with human blood cells suspended in autologous serum and kinetics of binding analysed. When purified polymorphonuclear (PMN) or mononuclear cells (MNC) were studied, maximum binding was observed within 8 min, and immune complexes (IC) remained associated with cells even after 1 hr. When cells were studied unseparated (in the same amount of serum), maximum binding was observed slightly earlier (within 4 min), but within 15 min most of the IC were found in the serum. Separation of cell types at the time of maximal binding and studies with cell preparations depleted of different elements revealed that binding was principally to red blood cells (RBC). IC recovered in the serum 16 min after addition to unseparated cells bound very slowly to purified PMN or MNC; binding after 30 min was 10-15% of that observed with fresh IC at 8 min. Ultracentrifugal analysis revealed that reduction in binding efficiency correlated with decrease in the size of IC. RBC isolated after binding and release of IC bound newly-formed IC was identical rapidity and capacity as fresh RBC, indicating that receptors were not altered by IC. Kinetics studies with serum in the absence of cells suggested that interaction with RBC accelerated the rate of change in binding properties of IC. Rates of binding and release were independent of antigen/antibody ratio but were slowed and binding to RBC sustained when diluted or hypocomplementaemic (SLE) serum was substituted for neat serum. Our results suggest that competition for IC by RBC is associated with loss of ability of IC to bind to other blood cell types and reduction in size of IC, and that abnormalities of complement can lead to prolonged association of IC with RBC.

Antigen-Antibody Complex↗