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Biomedical subjects

A T Reder

Publications and source records attributed to A T Reder.

At least 55 records · Page 3Linked to original sources
PubMed1990

Sympathetic skin responses are decreased and lymphocyte beta-adrenergic receptors are increased in progressive multiple sclerosis.

Immune abnormalities, including deficient CD8 lymphocyte-mediated suppression, have been implicated in the progression of multiple sclerosis (MS). The peripheral sympathetic branch of the autonomic nervous system innervates the lymphoid organs and affects immune function. Animals with an ablated sympathetic nervous system develop more severe experimental allergic encephalomyelitis than control animals and exhibit an increased density of beta-adrenergic receptors on their lymphocytes. Experimental allergic encephalomyelitis shares many features with MS. Accordingly, we investigated the psychogalvanic skin reflex in patients with rapidly progressive MS and found that 13 patients (57%) lacked this sympathetic-mediated response. The density of beta-adrenergic receptors on lymphocyte subsets was increased in progressive MS, most notably on the CD8 suppressor/cytotoxic subset. B lymphocytes had the greatest number of receptors with 12.1 +/- 1.8 fmol/10(6) cells in control subjects and 18.7 +/- 2.6 fmol/10(6) cells in patients with MS. CD8 lymphocytes possessed an intermediate number of receptors with 3.4 +/- 0.4 fmol/10(6) cells in control subjects and 9.1 +/- 1.6 fmol/10(6) cells in patients with MS. CD4 lymphocytes demonstrated the fewest receptors with 1.2 +/- 0.1 fmol/10(6) cells in control subjects and 1.8 +/- 0.4 fmol/10(6) cells in patients with MS. No differences in the affinity or function (cyclic adenosine monophosphate levels in response to 10(-5) M (-)isoproterenol) of the adrenergic receptor were found when patients with progressive MS and control subjects were compared. Autonomic abnormalities in progressive MS and the increased beta-adrenergic receptor density found on CD8 lymphocytes may be related.

Adult↗
PubMed1988

Comparison of in vivo and in vitro glucocorticoid sensitivity in depression: relationship to the dexamethasone suppression test.

The effect of in vivo (1 mg) and in vitro (10(-7)-10(-10) M) dexamethasone administration on mitogen-induced lymphocyte proliferation was examined in drug-free depressed patients, nondepressed psychiatric patients, as well as normal controls, and was related to the results of a standard overnight Dexamethasone Suppression Test (DST). The effect of oral dexamethasone administration was also examined for its effect on lymphocyte cytosolic glucocorticoid receptor content. Oral dexamethasone administration significantly decreased both phytohemagglutinin (PHA) and concanavalin A (Con-A) induced lymphocyte proliferation, as well as glucocorticoid receptor number in suppressors, whereas dexamethasone failed to decrease these responses in nonsuppressors. Nonsuppressors had significantly lower serum dexamethasone levels compared to suppressors at both 8:00 AM and 4:00 PM. However, when differences in serum dexamethasone levels were covaried out, there were still significant differences between suppressors and nonsuppressors on the dexamethasone-induced mitogen changes, but the changes in glucocorticoid receptor content were no longer significant. In vitro incubation of lymphocytes with dexamethasone produced a dose-related decrease in mitogenesis, which was not different between the depressed and nondepressed groups. However, at physiologically relevant concentrations of dexamethasone (10(-9)-10(-10) M), nonsuppressors as compared to suppressors were more resistant to the immunosuppressive effects of in vitro dexamethasone on the Con-A response. The inhibitory effect of in vitro dexamethasone on Con-A-stimulated lymphocytes was positively correlated with basal 4:00 PM cortisol values. In conclusion, in vitro techniques are useful probes to assess glucocorticoid sensitivity in depression. The present results also further support the hypothesis that glucocorticoid insensitivity is associated with DST nonsuppression.

Adult↗
PubMed1987

Susceptibility of astrocytes to class I MHC antigen-specific cytotoxicity.

Cell-mediated immune mechanisms contribute to tissue injury within the central nervous system (CNS) in a number of experimental diseases, including experimental allergic encephalomyelitis and some viral infections, and may mediate lesion formation in multiple sclerosis. We investigated the conditions under which murine astrocytes can become susceptible targets of cytotoxic T cells. We demonstrate that mouse astrocytes in vitro can be susceptible targets of class I major histocompatibility complex (MHC)-specific cytotoxicity mediated by L3 cytotoxic T lymphocytes (CTL). Expression of appropriate class I MHC antigen on the astrocytes is a requirement, because only cells bearing the H-2d phenotype are susceptible to lysis by L3 cells. BALB/c-H-2dm2 astrocytes lacking the specific determinant recognized by L3 cells are not susceptible to lysis. Astrocyte lysis can, however, occur under culture conditions in which MHC antigen expression is immunocytochemically low or undetectable. Cytolysis can be inhibited by pretreatment of the effector L3 cells with either anti-Lyt-2 monoclonal antibody (mAb) or anti-clonotypic mAb and by preincubation of the glial target cells with an appropriate anti-H-2 antibody (anti-H-2Ld). mAb to lymphocyte function-associated antigen does not inhibit cytotoxicity of the L3 clone against glial cells. Knowledge regarding the role of CTL within the CNS, including the surface molecules involved in glial cell lysis, could further the development of immunotherapies designed to effect immune reactivity within the CNS.

Animals↗
PubMed1987

Molecular analysis of the CD8 gene in multiple sclerosis.

Analysis of DNA fragments of the CD8 gene following digestion with three restriction enzymes showed no differences between patients with chronic progressive multiple sclerosis (MS), familial MS and controls. These abnormalities suggest that any abnormalities in the expression of CD8 protein in MS are not likely to be due to a gross deletion or rearrangement of the CD8 gene.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Dexamethasone suppression test abnormalities in multiple sclerosis: relation to ACTH therapy.

We studied the 1-mg overnight dexamethasone suppression test (DST) in patients with MS. In about 50% of patients, serum cortisol did not fall below 5.0 micrograms/dl. This percentage was similar in patients with major depression, but contrasted to 11% in normal controls. MS nonsuppressors were not more depressed than suppressors; dexamethasone bioavailability may have contributed because nonsuppressors had lower serum dexamethasone levels than suppressors. Suppressors improved in the week following ACTH therapy; nonsuppressors did not. Furthermore, serum dexamethasone values correlated positively with clinical response to ACTH treatment. The DST may be a useful neuroendocrine test of glucocorticoid sensitivity in MS patients.

Adrenocorticotropic Hormone↗
PubMed1986

Neuroleukin: a lymphokine product of lectin-stimulated T cells.

Neuroleukin is a lymphokine product of lectin-stimulated T cells that induces immunoglobulin secretion by cultured human peripheral blood mononuclear cells. Neuroleukin acts early in the in vitro response that leads to formation of antibody-secreting cells, but continued production of immunoglobulin by differentiated antibody-secreting cells is neuroleukin-independent. Although the factor is not directly mitogenic, cellular proliferation is a late component of the response to neuroleukin. Neuroleukin does not have B-cell growth factor (BCGF) or B-cell differentiation factor (BCDF) activity in defined assays. Neuroleukin-evoked induction of immunoglobulin secretion is both monocyte- and T-cell-dependent.

Animals↗
PubMed1986

An epitope shared by central nervous system myelin and peripheral blood macrophages.

Lewis rats were immunized with a homogenate of human spinal cord. Splenocytes from the immunized rats were fused with cells from the SP2/0-Ag14 cell line to form hybrids that were subsequently screened immunohistochemically for secretion of antibodies against myelin. Thirty hybrids secreting anti-myelin antibodies were cloned. One secreted antibody (774) that immunohistochemically stained central nervous system (CNS) myelin but not peripheral nervous system (PNS) myelin also bound to the surface of peripheral blood macrophages. Hence we have identified an epitope that is shared by peripheral blood macrophages and CNS myelin.

Animals↗
PubMed1986

Comparison of T8+ cell-mediated suppressor and cytotoxic functions in multiple sclerosis.

Patients with progressive multiple sclerosis (MS) and controls were compared with regard to: (a) in vitro pokeweed mitogen (pwm)-induced IgG secretion, as an indirect measure of T8+ cell-mediated suppressor function; (b) alloantigen-directed cytotoxic activity, a predominantly T8+ cell-mediated function. The MS group had increased IgG secretion (4790 +/- 372 ng/ml vs. 1866 +/- 233 ng/ml, P less than 0.001) compared to controls. In contrast, alloantigen-directed cytotoxic activity did not differ between MS and control groups. These results suggest a selective defect of suppressor cell function in MS rather than a generalized dysfunction of T8+ cells. Defective immunoregulatory control coupled with preserved effector functions may contribute to the autoimmune process, suspected to underlie the pathogenesis of MS.

Adult↗
PubMed1986

Suppressor and cytolytic cell function in multiple sclerosis. Effects of cyclosporine A and interleukin 2.

Patients with progressive multiple sclerosis (MS) demonstrated persistent reductions in levels of concanavalin A (Con A)-induced suppressor activity and heightened levels of in vitro pokeweed mitogen (PWM)-induced IgG secretion. The reduced Con A suppressor activity could not be reversed by addition of interleukin 2 (IL-2). Cyclosporine A (CsA) treatment did not alter the defect in Con A-induced suppressor activity, but did markedly inhibit T8+ cell-mediated alloantigen directed cytolytic activity; this latter defect was reversible by in vitro addition of IL-2. CsA-treated patients did not differ from placebo-treated patients with regard to levels of PWM-induced IgG secretion or proliferative responses of their mononuclear cells to Con A. The results indicate that CsA treatment of MS patients reduces cytolytic function from baseline normal values, but does not alter aberrant suppressor cell function.

Adult↗
PubMed1986

Dissociation of T8+ cell-mediated cytolytic and suppressor functions in young adults.

In the normal young adult population, in vitro levels of polyclonally-induced IgG secretion by mononuclear cells (MNCs) vary widely amongst individuals. Levels of IgG secretion correlate with functional suppressor activity of T8+ cells but not with their proportion within the MNCs either prior to culture, or as found in this study, at the end of the culture period. The current study also demonstrates a lack of correlation between T8+ cell-mediated suppressor (Ts) function and a second predominantly T8+ cell-mediated function, alloantigen-directed cytolytic (Tc) activity. Whether this dissociation between Ts and Tc functions reflects quantitative differences in subsets contained within the T8+ population or qualitative differences in the mechanisms required for induction or generation of Ts and Tc remains to be established.

Adult↗
PubMed1985

Age-related changes in mechanisms accounting for low levels of polyclonally induced immunoglobulin secretion in humans.

The mechanisms accounting for low levels of T-cell-dependent polyclonal IgG secretion in old and young human adults were compared. In elderly donors, in contrast to young donors, low levels of IgG secretion by unfractionated mononuclear cells (MNCs) did not correlate with functional suppressor activity of "panning"-enriched T8+ cells. Levels of IgG secretion by MNCs did not correlate either with proportions of T8+ or T4+ cells in the MNC population or with the functional helper activity of panning-enriched T4+ cells, in either old or young age groups. In young donors suppression mediated by either 2 or 5 X 10(4)T8+ cells of "low" IgG secretors (80.2 +/- 4.8 and 90.2 +/- 1.9%) was significantly greater than that induced by T8+ cells of "high" secretors (41.8 +/- 5.7 and 71.0 +/- 4.0%). Among elderly donors, suppression mediated by either 2 or 5 X 10(4)T8+ cells was reduced in both the low IgG secretion (31.9 +/- 5.3 and 52.3 +/- 7.0%) and high IgG secreting (14.9 +/- 7.2 and 46.8 +/- 5.7%) compared to the corresponding young donor subgroup. Levels of suppression mediated by 2 X 10(4)T8+ cells were suggestively lower in the high IgG secreting elderly subgroup compared to the low secreting subgroup (P less than 0.1). Our data suggest that decreased suppressor activity is a generalized occurrence in aging and that low polyclonal T-dependent MNC IgG secretion in the elderly, in contrast to young adults, cannot be attributed to high T-suppressor activity; nor does it usually reflect defective T-helper activity.

Adolescent↗
PubMed1985

Glucocorticoid receptors in depression: relationship to the dexamethasone suppression test.

Cytoplasmic glucocorticoid receptor content wa quantitated in lymphocytes from unmedicated depressed patients and control subjects before and after a standardized dexamethasone suppression test. Depressed patients (N = 11) had significantly lower (32%) basal cytoplasmic glucocorticoid receptor content than the control group (N = 14). Suppression of serum cortisol (5.0 micrograms/dl or less) in both control and depressed subjects (N = 16) following dexamethasone (1 mg) was associated with a decrease in lymphocyte cytoplasmic glucocorticoid receptor number, whereas no such change occurred in cortisol nonsuppressors (N = 9). Changes in receptor concentration were positively correlated with postdexamethasone serum cortisol levels and with the inhibitory effect of dexamethasone on mitogen-induced lymphocyte proliferation.

Adult↗
PubMed1985

Senile dementia of Alzheimer's type (SDAT): reduced T8+-cell-mediated suppressor activity.

We compared patients with senile dementia of the Alzheimer's type (SDAT) and age-matched controls with respect to T8+-cell-mediated suppressor function using a pokeweed mitogen (pwm)-induced IgG secretion assay. The responding B cells were allogeneic to the T-regulator cells. T8+-cell-mediated suppression was lower in SDAT patients than the controls when we used either 2 X 10(4) or 5 X 10(4) T8+ cells. Suppressor function was lower in both SDAT and elderly controls than in young adults. SDAT patients and controls did not differ with regard to T4+-cell-mediated helper activity. In SDAT patients, there seems to be an exaggeration of the age-related decline in suppressor-cell function. Whether such changes reflect accelerated changes of intrinsic lymphocyte properties or aberrant neural influences on lymphocytes remains to be resolved.

Aged↗
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↗