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W Stohl

Publications and source records attributed to W Stohl.

49 records · Page 3Linked to original sources
PubMed1987

Inhibition of T cell-dependent human B cell proliferation and B cell differentiation by polyspecific monomeric IgG.

A commercially available polyspecific, monomeric IgG preparation suitable for intravenous administration (IgSRK; Sandoglobulin) can inhibit pokeweed mitogen (PWM)-induced proliferation of peripheral blood mononuclear cells (PBMC) by a small, but statistically significant, amount compared to control cultures. Such inhibition could not be demonstrated when PBMC were stimulated with the T cell mitogen phytohaemagglutinin. Surface phenotype analysis of the PWM-stimulated cells indicated that in IgSRK-containing cultures, the proportion of B cells was decreased and the proportion of T cells was increased compared to control cultures. This alteration in T:B ratio was not due to antigenic modulation of B or T cell markers from their surfaces. In addition, IgSRK inhibited the proliferation of T cell-depleted PBMC cultures stimulated by B cell proliferation factors (BCPF) but not by fixed protein A-bearing Staphylococcus aureus strain Cowan I. The capacity to inhibit B cell proliferation was independent of and distinct from its capacity to inhibit B cell differentiation, since IgSRK inhibited the differentiation of a B cell differentiation factor (BCDF)-sensitive line by BCDF (which contains no BCPF activity). IgSRK inhibited PWM-induced generation of cytoplasmic Ig+ cells but had no effect on Ig secretion from mature Ig-secreting cells. Taken together, these findings suggest that IgSRK (which contains the IgG fraction from pooled plasma from 2,000 healthy donors) can inhibit T cell-dependent or T cell factor-dependent B cell proliferation and B cell differentiation.

B-Lymphocytes↗
PubMed1986

Cellular mechanisms in the in vitro inhibition of pokeweed mitogen-induced B cell differentiation by immunoglobulin for intravenous use.

Polyspecific monomeric IgG for i.v. use (IgSRK; Sandoglobulin) can inhibit in vitro pokeweed mitogen (PWM)-induced B cell differentiation. This antigen-nonspecific inhibition is an early event, because removal of the IgSRK from cultures of PWM-stimulated peripheral blood mononuclear cells (PBMC) after as short a period as 24 hr could not reverse the inhibitory effects. Furthermore, replacement of the IgSRK-exposed T cells after 48 hr of culture with fresh autologous T cells could not abrogate the inhibition. In addition, IgSRK exerted an inhibitory effect on non-T cells even before their activation by PWM. Neither augmentation of T suppressor activity nor inhibition of T helper activity could be demonstrated as a consequence of interaction with IgSRK. Irradiation of the T cells before culture, supplementing the culture medium with exogenous interleukin 2, monocyte depletion, or depletion of the Leu-11+ population had no effect on the IgSRK-mediated inhibition. Tonsil cells were as susceptible to the inhibitory effects of IgSRK as were unseparated PBMC. Taken together, these experiments point to a direct inhibitory effect of IgSRK on the B cell in this antigen-nonspecific system. However, minor roles for monocytes, T cells, and/or Leu-11+ cells cannot be excluded. This inhibitory capacity of IgSRK might be efficacious clinically in the treatment of autoimmune disorders in which pathogenic autoantibodies play a role. However, such treatment might also inhibit desired antibody responses to vaccinations and/or infectious agents.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Modulation of the immune response by immunoglobulin for intravenous use. II. Inhibitory effects of sera from treated patients.

Sera were collected from patients with common varied immunodeficiency (CVI) prior to and following intravenous gamma-globulin (IVGG) infusion. Cultures of pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells from normal donors in medium containing post-IVGG infusion sera generated significantly fewer plaque-forming cells (PFC) than those cultures in medium containing the corresponding pre-IVGG infusion sera. However, preinfusion CVI sera were found to be similar to normal sera in their capacities to support PWM-induced PFC generation, despite the disparity in Ig levels between the two groups of sera. Furthermore, serum collected from a CVI patient 24 hr or more after IVGG infusion no longer possessed the same inhibitory capacity as serum collected 10 min after IVGG infusion despite elevated IgG levels compared to baseline. These studies suggest that IVGG infusion may induce an immunosuppressive effect which is transient in nature, raising the possibility of in vivo counterbalancing homeostatic mechanisms responding to this immune perturbation.

Antibody-Producing Cells↗
PubMed1985

Systemic lupus erythematosus with deficiency of the T4 epitope on T helper/inducer cells.

Three black Jamaicans with systemic lupus erythematosus (SLE) were identified whose T helper/inducer cells lacked the T4 epitope (T4 epitope-deficient phenotype). All three patients had lymphadenopathy as part of their syndromes. The asymptomatic and otherwise healthy T4 epitope-deficient brother of one of these patients also had lymphadenopathy in a distribution identical to that of his sister with SLE. Family studies pointed to an autosomal codominant mode of inheritance not linked to the HLA locus for the T4 epitope phenotype. Cultures of peripheral-blood mononuclear cells revealed impaired B-cell differentiation upon stimulation with pokeweed mitogen in cells originating from the T4 epitope-deficient family members as compared with those originating from their T4 epitope-intermediate relatives. Ratios of T helper/inducer cells to T suppressor/cytotoxic cells, the presence of various autoantibodies, and proliferation in response to mitogens and in the mixed lymphocyte reactions did not correlate with T4 epitope phenotype. We suggest that SLE in association with the T4 epitope-deficient phenotype may represent a unique subset of patients with SLE that has distinct clinical and immunologic properties.

B-Lymphocytes↗
PubMed1985

Modulation of the immune response by immunoglobulin for intravenous use. I. Inhibition of pokeweed mitogen-induced B cell differentiation.

The effect of a commercially available intravenous gammaglobulin preparation (IgSRK; Sandoglobulin) on the antigen-non-specific activation of the immune system was examined using pokeweed mitogen (PWM)-induced B cell differentiation. In cultures of peripheral blood mononuclear cells from 16 normal donors, IgSRK (300 micrograms/ml) inhibited PWM-induced generation of plaque-forming cells by 76% (P less than 0.001), whereas human serum albumin (300 micrograms/ml) induced no significant inhibition (5%; P not significant). The IgSRK-mediated suppression was demonstrable in both serum-containing (76%) and serum-free (63%) media, and monomeric IgSRK suppressed as effectively as did heat-aggregated IgSRK. F(ab')2 fragments exhibited no inhibitory capacity (mean inhibition -11%; P not significant) suggesting that the Fc portion of IgSRK may be required for suppression. In addition, IgSRK had to be added to the cultures at their initiation to effect full inhibition. These studies suggest a potential beneficial pharmacological role for IgSRK in the treatment of disorders characterized by pathogenic autoantibodies, but also warn of a potential deleterious effect of inhibiting the host's humoral response to an infectious challenge.

Antibody-Producing Cells↗
PubMed1984

Heterogeneity in expression of the T4 epitope in black individuals.

The T-cell differentiation antigen T4/Leu3 has been described as a non-polymorphic molecule important in T-cell recognition of class II major histocompatibility complex antigens. We report the polymorphism of this molecule in black individuals as manifest by a heterogeneity of staining with OKT4 monoclonal antibody. No such heterogeneity was observed when staining with other monoclonal antibodies that bind to different epitopes of the same molecule. No heterogeneity of staining with any of the monoclonal antibodies was observed in whites. Three patterns of OKT4 staining emerged: intact, deficient, and intermediate. This heterogeneity is likely to be due to an intrinsic heterogeneity in T4 epitope expression and not secondary to an interfering plasma factor as shown by the preservation of the T4 epitope pattern after a 3-day culture in the presence or absence of mitogen. Family studies strongly suggest that this heterogeneity in T4 epitope expression is inherited in an autosomal codominant fashion.

Africa↗
PubMed1979

A quantitative assay for experimental allergic encephalomyelitis in the rat based on permeability of spinal cords to 125I-human gamma-globulin.

We have developed a quantitative assay for experimental allergic encephalomyelitis (EAE) in the rat based on permeability of the spinal cord to 125I-human gamma-globulin (HGG). This assay is highly reproducible and eliminates many of the drawbacks of assaying for EAE on the basis of clinical and/or histologic criteria. Using the assay, we have shown a direct correlation between onset of histologic changes in the spinal cord and onset of permeability changes in the spinal cord. No rat without histologic lesions manifest permeability alterations, and all rats with histologic lesions did manifest increased permeability to 125I-HGG. Furthermore, strains of rats susceptible to EAE demonstrated permeability changes, whereas resistant rats did not. In addition, we demonstrated by permeability and histologic criteria that guinea pig myelin basic protein emulsified with incomplete Freund's adjuvant is encephalitogenic in the Lewis rat. We also demonstrated that recipients of passive transfer of sensitized cells develop permeability changes along with histologic lesions. We conclude that measuring permeability to 125I-HGG in the spinal cords of rats is a valid assay for EAE, and its improves upon current indices of EAE in that it is readily quantifiable.

Animals↗
PubMed1978

Chronic permeability of the central nervous system to mononuclear cells in experimental allergic encephalomyelitis in the Lewis rat.

In order to assess whether experimental allergic encephalomyelitis (EAE), a putative animal model for multiple sclerosis (MS), is an ongoing chronic disorder, we have studied the permeability of spinal cords of Lewis rats with EAE to 3H-uridine- or 3H-thymidine-labeled lymphoid cells obtained from thymuses of naive donors or from draining lymph nodes of donors injected with guinea pig spinal cord + complete Fruend's adjuvant (CFA), guinea pig myelin basic protein + CFA, or with CFA alone. During the acute clinical phase of EAE there is a high-level infiltration of 3H-thymidine- or 3H-uridine-labeled cells into the spinal cords. After clinical recovery from EAE up to 58 days post-inoculation, there is a low-level infiltration of 3H-thymidine-labeled cells into the spinal cords. A similar infiltration into the spinal cords by 3H-uridine-labeled cells was not detected. Donor cells from animals immunized with CFA alone showed similar levels of infiltration into the spinal cords of animals with EAE as donor cells from animals immunized with the encephalitogenic emulsion. Spinal cords from recipients immunized with CFA alone showed no increased permeability to labeled cells. Heat-killed labeled cells did not migrate into the spinal cords of animals with EAE. We conclude that a) EAE is a chronic disease and in this regard is a valid model for MS; and B) in the chronic phase of EAE, recently divided cells (3H-thymidine-labeled cells) show higher levels of migration into the target tissue than 3H-uridine-labeled cells.

Animals↗
PubMed1977

Distribution of the thy-1 antigen in cellular and subcellular fractions of adult mouse brain.

By using a cytotoxicity inhibition assay employing AKR anti-C3H thymocyte antiserum, we have determined the degree of expression of the thy-1 antigen in fractions of adult mouse brain. As expressed as cytotoxicity inhibitory capacity per mg protein with C3H whole brain arbitrarily assigned a value of 1.0, the following values were found: C3H cerebral cortex, 5.8; C3H cerebral cortex synaptosomes, 2.5: C3H whole brain myelin, 0.65; C3H cerebral cortex neurons, 0.16; and C3H cerebral cortex mitochondria 0.10. Neither C1300 neuroblastoma cells nor any AKR neural fraction had detectable levels of thy-1. The findings indicate that the thy-1 antigen is found mainly in mouse cerebral cortex and in synaptosomal fractions, whereas myelin fractions contain lower but perhaps significant amounts of thy-1. Cerebral cortex neurons, isolated by a method requiring a 90-min mild trypsinization at 37 degrees C, did not display significant amounts of the thy-1 antigen. These results lend themselves to further study in the area of differentiation and development of central nervous system components and in the area of central nervous system immunopathology.

Animals↗