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Biomedical subjects

A Reder

Publications and source records attributed to A Reder.

6 recordsLinked to original sources

The effect of chemical sympathectomy on natural killer cells in mice.

The nervous system affects immune regulation. We permanently ablated the sympathetic nervous system (SNS) of CBA mice with 6-OHDA at birth. Function of splenic natural killer (NK) cells in the sympathectomized mice was equivalent to controls at 2 weeks, but rose significantly above control levels at 4 weeks. NK cell function decreased below control values thereafter. NK cell numbers paralleled these changes in NK cell function. Our data suggest that the SNS may regulate the number and function of splenic NK cells during development.

Aging

Activated suppressor cell function in multiple sclerosis--clinical correlations.

Activated suppressor cell function mediated by either freshly isolated peripheral blood mononuclear cells (MNCs), freshly isolated CD8+ lymphocytes or by CD8+ cell lines, has previously been found to be reduced compared to controls in multiple sclerosis (MS) patients with progressive disease (MS-P). In this study, we found that suppressor activity mediated by CD8+ cell lines, derived from MS patients with stable disease (MS-S) patients and maintained in culture for 14 days, was significantly greater (45 +/- 6%) compared to that mediated by MS-P patients' CD8+ cells (11 +/- 4%, P less than 0.005). The MS-S suppressor values were, however, suggestively reduced compared to controls (60 +/- 6%, P less than 0.05). MNC-mediated suppressor values for the MS-S group (61 +/- 5%) did not differ from the control group (67 +/- 6%). Values for the MS-P group (7 +/- 6%) were significantly reduced compared to MS-S and control groups. Cytotoxic activity mediated by CD8+ cell lines showing defective suppressor function did not differ from control values. The cell lines in MS and control did not differ with respect to their rate of proliferation in the presence of IL-2 and OKT3. Suppressor function in this assay was ablated if exogenous IL-2 was removed from the culture media. These data suggest that defective activated suppressor function is characteristic of the progressive form of MS, although a suppressor defect is also partially expressed in stable MS patients when CD8+ cell lines are studied.

Adult

Activated suppressor cell dysfunction in progressive multiple sclerosis.

Concanavalin A (Con A)-induced suppressor activity has previously been shown to be reduced in multiple sclerosis (MS) patients with active clinical disease. In this study, we demonstrate that OKT3, as well as Con A induced suppressor activity mediated by unfractionated peripheral blood mononuclear cells is reduced in patients with the progressive form of MS. By performing reconstitution experiments involving E+, T4+, or T8+ cells derived from either MS patients or controls, and normal allogeneic macrophages or E- cells, we sought to define the cellular basis for this suppressor defect. In both MS and control groups, E+ cells were required to obtain measurable levels of suppression. Suppressor levels induced by Con A-activated cultures containing E+ cells from MS patients were lower than those induced by those containing control donor E+ cells. Suppression mediated by T8+ cells from MS patients was also lower than for controls. In the control group, suppression mediated by T8+ cells exceeded that mediated by T4+ cells; such differences were not apparent in the MS group. These results suggest that although Con A-induced suppression can be mediated by a number of T and non-T cell subsets, the functional suppressor defect measured in the MS population does involve the T8+ cell subset.

Adult

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

B-cell differentiation in multiple sclerosis and the effect of intravenous ACTH.

B-cell differentiation was studied in patients with MS and in age- and sex-matched controls, using a pokeweed mitogen (PWM)-stimulated in vitro culture system. Peripheral blood lymphocytes were obtained and separated into T-cell and non-T-cell fractions. Autologous and allogeneic combinations of T cells and B cells were cultured in the presence of pokeweed mitogen for 7 days. Numbers of plaque-forming cells (PFC) were measured at the end of the culture period. T cells from MS patients before and after a 10-day course of adrenocorticotropic hormone (ACTH) were able to cooperate fully in the generation of PWM-generated PFC. B cells from MS patients showed a decreased ability to differentiate into PFC in the presence of either autologous or allogeneic T cells. No significant change in differentiation was observed after a 10-day course of intravenous ACTH. We were thus unable to demonstrate any alteration in T-cell function in MS but were able to demonstrate a decreased ability of MS B cells to differentiate into immunoglobulin-secreting cells. ACTH had no significant effect on these abnormalities.

Adrenocorticotropic Hormone