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Biomedical subjects

R Benner

Publications and source records attributed to R Benner.

At least 109 records · Page 6Linked to original sources
PubMed1987

Cellular and humoral immunity in patients with hyperthyroid Graves' disease before, during and after antithyroid drug treatment.

Many reports of thyroid stimulating immunoglobulins (TSI) in relation to treatment of Graves' disease have been published and with variable results concerning prediction of permanent remission or relapse after therapy. A range of methods has been used and little has been published measuring TSI by using their ability to stimulate cyclic AMP production in human thyroid cells in monolayer culture. We therefore conducted a prospective study of the predictive value of such an assay in patients with hyperthyroid Graves' disease before, during and after treatment of one year with methimazole and thyroid hormone substitution. Furthermore, the possible relationship between activated suppressor T lymphocytes and TSI in patients followed before, during and after medical therapy has been studied. Patients were divided into two groups; group I, 15 patients, who stayed in remission and group II, 14, who relapsed during the first year after discontinuation of therapy. Mean TSI activity did not differ between the two groups before and during the first half year of medication. In the second half year of treatment, however, mean TSI activity was significantly lower in group I. TSI activity at the end of treatment appeared to have no value in predicting final outcome. Increased TSI activity in group II during treatment was reflected in an increased pertechnetate thyroidal uptake as compared to that in group I. There was no relationship between changes in TSI activity and T cell subsets (Leu 1, 2a, 3a). We found no difference in T lymphocytes between the two groups at any time during observation. Subsets of T lymphocytes in both patient groups did not differ from normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Suppression of delayed-type hypersensitivity to histocompatibility antigens by ultraviolet radiation.

Delayed-type hypersensitivity (DTH) reactions to allogeneic histocompatibility antigens in mice could be systemically suppressed by a single exposure to UV-B irradiation. The extent of suppression reached its maximum 4 days after irradiation, gradually waned thereafter, and disappeared at Day 21. Re-exposure of these mice to UV-B after waning reinduced the state of suppression. The suppression could be transferred to naive mice by means of splenic T lymphocytes. The suppressor T (Ts) cells suppressed the proliferative activity in the lymph nodes draining the site of immunization, but not the activity of already activated DTH-reactive T cells. Phenotypical analysis of these Ts cells revealed that two subpopulations of T cells are involved: one with the Lyt-1+, 2- phenotype, the other with the Lyt-1-, 2+ phenotype.

Animals↗
PubMed1987

The influence of H-2 genetic factors on the development of benign monoclonal gammopathy in ageing H-2 congenic C57BL and BALB mice.

The role of H-2 genetic factors in the development of benign monoclonal gammopathy (BMG) was investigated in six H-2 congenic C57BL and BALB strains (C57BL/10.ScSn and BALB.B: H-2b; B10.D2 and BALB/c: H-2d; B10.BR and BALB.K: H-2k) during ageing. The frequencies of homogeneous immunoglobulins (H-Ig), both single and multiple, in the three C57BL strains were higher than those in the corresponding three BALB strains. No relationship was found with a particular H-2 haplotype. The most frequent H-Ig isotype within the C57BL strains was IgG2a, within BALB.B and BALB.K mice IgG3 and in BALB/c mice IgG1. Categorization of the monoclonal gammopathies (MG) on the basis of their origin showed a single transient monoclonal B-cell proliferation in 2-5% and 3-9% of the C57BL and BALB mice positive for H-Ig, respectively. Multiple myeloma or B-cell lymphoma were found to be responsible for about 1% of the paraproteinaemias in all strains. Persistent, non-progressive MG, most likely BMG, was detected in 70-81% and 39-46% of the C57BL and BALB mice positive for H-Ig, respectively. The remaining 14-24% and 50-58% of the, respectively, C57BL and BALB mice positive for H-Ig could not be evaluated in time. The H-2 haplotypes under investigation were not associated with the onset, occurrence, multiplicity, persistence or isotype of the MG developing in these H-2 congenic C57BL and BALB strains during ageing.

Aging↗
PubMed1987

The effect of corticosteroids upon murine B cells in vivo and in vitro as determined in the LPS-culture system.

The influence of the synthetic corticosteroid dexamethasone sodium phosphate (DEXA) upon mouse B cells was studied. This was done by in vivo treatment of mice with a single or multiple injection of DEXA, and by culturing murine spleen cells and bone marrow cells in vitro in the presence of different concentrations of DEXA. The effect of DEXA on the B-cell compartment was assayed by polyclonal stimulation of the B cells by Escherichia coli lipopolysaccharide (LPS) in vitro and subsequent measurement of the Ig-secreting cell response in the protein A plaque assay. DEXA treatment could greatly reduce the number of B cells in the spleen, but the bone marrow B-cell compartment was quite resistant to DEXA. The in vitro LPS-induced IgM response of the residual B cells from both spleen and bone marrow and their capacity to switch from IgM to IgG and IgA secretion were not affected. These data indicate that DEXA can decrease the total number of B cells but not the functional capacity of the residual LPS-reactive B cells. This was confirmed at the clonal level by limiting dilution culture experiments. The contrasting effects of DEXA on splenic and bone marrow B cells was also found when the cells were exposed to the drug in vitro. It was found that 10(-8) M DEXA in vitro reduced the response of splenic B cells to LPS by more than 80%, while a similar reduction of the response by bone marrow B cells required a 1000-fold higher concentration.

Animals↗
PubMed1986

Characterization of an Lyt-2+ alloreactive cytotoxic T cell clone specific for H-2Db that cross-reacts with I-Ek.

An alloreactive cytotoxic T cell clone (433) possessing the L3T4-, Lyt-2+ phenotype is described that shows a double specificity. It has been derived from unprimed BALB/c (H-2d) spleen cells by repetitive in vitro restimulation with C57BL/6(H-2b) cells. The specificity of clone 433 was determined in cytotoxicity and proliferation experiments. One specificity was for the class I antigen H-2Db and the second was for the class II antigen I-Ek. Inhibition of cytotoxicity with monoclonal antibodies confirmed these results. Cold target competition experiments demonstrated that the two specificities were mediated by the same cell population. Anti-Lyt-2 antibodies inhibited only the H-2Db- but not the I-Ek-specific lysis, suggesting a higher affinity of the antigen receptor for I-Ek than for Db. To our knowledge, this is the first description of a T cell clone that is specific for a class I antigen and cross-reacts heteroclitically with a class II antigen.

Animals↗
PubMed1986

Suppression of antigraft immunity by preimmunization. III. Characterization of suppressor T cells involved in suppression of the efferent phase of DTH against alloantigens.

Suppressor T (Ts) cells that can suppress delayed type hypersensitivity (DTH) against histocompatibility (H) antigens can be isolated from spleen and lymph nodes a few days after i.v. immunization of mice with irradiated allogeneic spleen cells. In this paper we investigated the suppression of the efferent phase of DTH to characterize the Ts cells involved, and to compare them with the afferent phase Ts cells that have been characterized in a previous paper of this series. The DTH against third party alloantigens that were not used for the i.v. suppressive immunization could be suppressed by presenting the third party alloantigens together with the original alloantigens in the challenge inoculum for eliciting the DTH reaction. Thus the ultimate suppressive effect by the Ts cells that are active during the efferent phase of DTH is nonspecific. This non-specific suppression of DTH to alloantigens has previously been found for the afferent phase Ts cells as well. For suppression of the efferent phase of DTH to alloantigens, a population of Lyt-1+2+ Ts cells appeared to be essential, just like in the suppression of the afferent phase of DTH to alloantigens. We did not find evidence for the involvement of cyclophosphamide-sensitive auxiliary Ts cells in suppression of the efferent phase of DTH. Also no evidence was found for H-2 or Igh-restricted activation and function of the Ts cells that were active during afferent and efferent phases of the DTH response to H antigens. In view of these similarities between afferent phase and efferent phase Ts cells we conclude that there are no arguments as yet to suppose that there is more than one type of T cells involved in the suppression of the afferent and efferent limb of DTH against H antigens.

Animals↗
PubMed1986

Joint inflammations and flare-up reactions in mice induced by a helper T cell clone.

Joint inflammation was induced in mice by cloned helper T cells specific for methylated bovine serum albumin (mBSA). This occurred after local injection of the helper T cells together with mBSA into the knee joint, but also when the helper T cells were intravenously injected and the antigen directly into the joint. Local injection of mBSA several weeks after waning of a joint inflammation induced by cloned helper T cells caused a flare-up reaction, indicating that the helper T cells persisted in the joint after the primary inflammation.

Animals↗
PubMed1986

'Background' Ig-secreting cells in pregnant germfree mice fed a chemically defined ultrafiltered diet.

During syngeneic pregnancy the numbers of 'spontaneously' occurring ('background') Ig-secreting cells were determined in the spleen, bone marrow (BM) and mesenteric lymph nodes (MLN) of BALB/c mice that were kept under germfree conditions and fed a low molecular weight synthetic diet (GF-CD), SPF BALB/c mice fed autoclaved natural ingredient (SPF-NI) and conventional BALB/c mice fed natural ingredient (CV-NI). 'Background' Ig-secreting cells were enumerated in the protein A plaque assay and the specificity repertoire of the IgM-secreting cells was determined with plaque assays specific for differently haptenized sheep red blood cells (SRBC). The numbers of 'background' Ig-secreting cells, especially the IgG- and IgA-secreting cells, are very much reduced in the BM and MLN of GF-CD mice as compared to SPF-NI and CV-NI mice. During pregnancy the total number of Ig-secreting cells increased in all lymphoid organs tested, but the proportional increase was most prominent for the IgG- and IgA-secreting cells in the BM and MLN of the GF-CD mice. This increase could only be due to their pregnant state since all environmental antigenic influences are excluded in GF-CD mice. No changes were found in the background specificity repertoire of the IgM-secreting cells during pregnancy. This suggests a polyclonal activation of the Ig-secreting cells during pregnancy. The reason for this activation remains obscure, but it has to be endogenous. Pregnancy apparently induces a new steady state of the immune system, which can be most properly investigated in GF-CD mice.

Animals↗
PubMed1986

Decreased in vivo functional T cell capacity in the murine autoimmune strains MRL/Mp-lpr/lpr and male BXSB/Mp.

We have studied the functional and proliferative capacity of the T cells of systemic lupus erythematosus (SLE)-prone MRL and BXSB mice during aging. The study was performed in vivo, in the delayed-type hypersensitivity (DTH) assay, and in vitro, in the mixed lymphocyte reaction (MLR). Both assays showed depressed T cell responses in MRL/l and male BXSB mice at 4 to 5 and 9 to 10 months of age, respectively, when a significant proportion of the animals showed clear-cut disease. At younger ages, the proliferation-dependent DTH was not affected in MRL/l and male BXSB mice. This is in agreement with the reported primary B cell defect of male BXSB mice, but not with the reported early T cell abnormalities in MRL/l mice. A subnormal reactivity of the highly proliferating T helper cells or the existence of a T cell subset with normal DTH reactivity might account for the relatively long-lasting normal DTH reactivity in MRL/l mice.

Animals↗
PubMed1986

Complement split product C5a mediates the lipopolysaccharide-induced mobilization of CFU-s and haemopoietic progenitor cells, but not the mobilization induced by proteolytic enzymes.

Intravenous (i.v.) injection of mice with lipopolysaccharide (LPS), and the proteolytic enzymes trypsin and proteinase, mobilizes pluripotent haemopoietic stem cells (CFU-s) as well as granulocyte-macrophage progenitor cells (GM-CFU) and the early progenitors of the erythroid lineage (E-BFU) from the haemopoietic tissues into the peripheral blood. We investigated the involvement of the complement (C) system in this process. It appeared that the early mobilization induced by LPS and other activators of the alternative complement pathway, such as Listeria monocytogenes (Lm) and zymosan, but not that induced by the proteolytic enzymes, was absent in C5-deficient mice. The mobilization by C activators in these mice could be restored by injection of C5-sufficient serum, suggesting a critical role for C5. The manner in which C5 was involved in the C activation-mediated stem cell mobilization was studied using a serum transfer system. C5-sufficient serum, activated in vitro by incubation with Lm and subsequently liberated from the bacteria, caused mobilization in both C5-sufficient and C5-deficient mice. C5-deficient serum was not able to do so. The resistance of the mobilizing principle to heat treatment (56 degrees C, 30 min) strongly suggests that it is identical with the C5 split product C5a, or an in vivo derivative of C5a. This conclusion was reinforced by the observation that a single injection of purified rat C5a into C5-deficient mice also induced mobilization of CFU-s.

Animals↗
PubMed1985

Frequency analysis of the antibody specificity repertoire of mitogen-reactive B cells and "spontaneously" occurring "background" plaque-forming cells in nude mice.

The antibody specificity repertoire of lipopolysaccharide (LPS)-reactive B cells has been determined in the spleens and bone marrow (BM) of C57BL/Ka athymic nude mice using a limiting dilution culture system that allows the growth and development of every LPS-reactive B cell into a clone of IgM-secreting cells. In addition, the numbers of "spontaneously" occurring ("background") IgM-, IgG-, and IgA-secreting cells as well as the "background" IgM antibody specificity repertoire has been assessed in spleens and BM. The frequencies of antigen-specific LPS-reactive B cells of C57BL/Ka nude and thymus-bearing mice showed a great similarity and ranged from 1 in 1000 to 1 in 2500 for sheep red blood cells (SRBC), horse red blood cells (HRBC), and goat red blood cells (GRBC), from 1 in 10 to 1 in 25 for 5-iodo-3-nitrophenyl-coupled (SRBC), from 1 in 15 to 1 in 150 for 4-hydroxy-3,5-dinitrophenyl-coupled SRBC, and from 1 in 70 to 1 in 140 for 2,4,6-trinitrophenyl-coupled SRBC. The specificity repertoire of the "background" IgM-secreting cells differed from that of age-matched thymus-bearing controls and was different in young and old C57BL/Ka nude mice. Within the limitations of having assessed only a minor fraction of the total B-cell antibody specificity repertoire and supposing that nude mice are largely devoid of functional T cells, the data presented suggest that the generation of the specificity repertoire of newly-formed B cells is hardly or not affected by T cells. On the other hand, T cells do affect the expression of the established repertoire, represented by "background" immunoglobulin-secreting cells.

Animals↗
PubMed1985

The long-lasting state of specific nonresponsiveness induced by intravenous immunization with alloantigens is due to the generation of recirculating suppressor T cells.

We investigated whether the long-lasting state of nonresponsiveness that is induced by intravenous immunization with alloantigens is mediated by suppressor T cells, or is caused by inactivation or deletion of the relevant alloreactive T cell clones. The data from parabiosis and thoracic duct drainage experiments suggest that the state of nonresponsiveness depends on recirculating non-proliferating Ts memory cells.

Animals↗
PubMed1985

Differential influence of 2'-deoxyguanosine on the induction and expression of suppressor T lymphocytes in vivo.

Subcutaneous (sc) immunization of mice with allogeneic spleen cells can induce delayed-type hypersensitivity (DTH) to histocompatibility antigens. Intravenous immunization with irradiated allogeneic spleen cells, on the other hand, induces suppressor T (Ts) lymphocytes. These Ts cells are capable of suppressing the host-versus-graft (HvG) DTH reactivity which normally arises after sc immunization. Moreover they can suppress the development of antihost DTH effector T cells during graft-versus-host (GvH) reactions. These models for HvG and GvH DTH reactivity were used to study the influence of 2'-deoxyguanosine (dGuo) on the induction, further development, and expression of Ts cells in vivo. It was found that administration of dGuo inhibits the proliferation-dependent induction and further development of Ts cells, but not the suppression mediated by already activated Ts cells.

Animals↗