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J D Taurog

Publications and source records attributed to J D Taurog.

At least 73 records · Page 4Linked to original sources
PubMed1983

The cellular basis of adjuvant arthritis. I. Enhancement of cell-mediated passive transfer by concanavalin A and by immunosuppressive pretreatment of the recipient.

Two reliable systems for the cell-mediated passive transfer of adjuvant arthritis have been developed. Donor rats were sensitized with Mycobacterium butyricum in mineral oil. In the first system, intravenous injection of adjuvant-sensitized donor lymph node or spleen cells into adult-thymectomized, lethally irradiated, bone marrow cell-reconstituted syngeneic rats induced arthritis in the recipients. In the second system, adjuvant-sensitized donor lymph node or spleen cells were cultured in vitro with concanavalin A; these cells induced arthritis in normal recipients as well as in thymectomized, irradiated, bone marrow cell-reconstituted recipients. The passively transferred disease in both systems resembled classical adjuvant-induced arthritis clinically, radiographically, and histologically. Neither irradiated, adjuvant-sensitized donor cells nor cells from donors not injected with complete adjuvant could passively transfer arthritis.

Animals↗
PubMed1983

The cellular basis of adjuvant arthritis. II. Characterization of the cells mediating passive transfer.

It has previously been reported that lymph node or spleen cells from rats with adjuvant-induced arthritis can transfer the disease to normal recipients after being cultured with concanavalin A (Con A). In this report, it is shown that a subpopulation of cells that (1) lack surface Ig and the antigen reactive with the monoclonal antibody OX8, (2) are largely nonadherent and esterase negative, and (3) are predominantly marked by the monoclonal antibody W3/25 can transfer arthritis after stimulation with Con A. Adjuvant-sensitized lymph node or spleen cells stimulated with Con A but not PHA transfer arthritis, and this difference correlates with relatively higher levels of interleukin 2 secretion by Con A-stimulated cells. A synthetic adjuvant, CP-20961, a substituted propanediamine, induces arthritis that is passively transferable under the same conditions as arthritis induced by classical mycobacterium-containing adjuvant. The data support the hypothesis that adjuvant inoculation in the rat results in the induction of a unique subpopulation of T cells that initiate the inflammatory joint disease.

Animals↗
PubMed1981

T cell abnormalities in NZB mice occur independently of autoantibody production.

By means of a series of crosses and backcrosses, ZB.CBA/N mice were prepared bearing largely NZB autosomal genes, but having X chromosomes derived only from CBA/N mice. The CBA/N X chromosome carries a gene, xid, that is associated with the lack of a B cell subset necessary for most of the spontaneous autoantibody production by NZB mice. These ZB.CBA/N mice failed to develop autoantibodies to T cells, erythrocytes, or DNA. The availability of mice that were mostly NZB, but which failed to make autoantibodies, especially anti-T cell antibodies, allowed us to study possible T cell regulatory defects in NZB mice in the absence of either antibodies reactive with such T cells or other autoantibodies. We found that such mice had derangements of T cell regulation as did the NZB mice. These observations strongly suggest that the t cell abnormalities of NZB mice are not caused by the B cell hyperactivity of these mice, but rather represent independent defects. Thus, NZB mice appear to have primary defects in both the B cell population and the T cell population. Whether or not these are separate, or derive from a common precursor cell abnormality, remains to be determined.

Animals↗
PubMed1981

Immunoregulation.

The immune system of higher vertebrates is a complex network of separate, interacting cell populations, each ontogenetically endowed with specific regulatory (inductive or suppressive) or effector functions. The products of at least two major gene clusters-the immunoglobulin structural genes and the genes of the major histocompatibility complex-are expressed as active and passive recognition structures on cells of the immune system and at least some of their secreted products. Macrophages play a critical role in the initiation of immune responses. Regulatory subsets of thymus-derived lymphocytes interact with macrophages and with each other in the control of immune effector cells. At every level of the immune response, cell interactions require that these regulatory cells recognize gene products of the major histocompatibility complex. Due to recent technical advances, rapid progress is being made in identifying subsets of human immunoregulatory cells; those identified to date show strong functional homology to previously well characterized murine cell subsets.

Animals↗
PubMed1980

Effect of CBA/N xid on spontaneous production of antibodies to DNA in MRL/1 and NZB backcross mice.

We have used the CBA/N X-linked B-cell maturation defect (xid) as a probe to analyse the B-cell subset involved in spontaneous anti-DNA production in MRL/1 and NZB mice. The presence of xid in NZB offspring significantly suppressed anti-DNA production, whereas it did not suppress spontaneously produced antibody to DNA in MRL/1 offspring. These studies suggest that largely non-overlapping B-cell subsets are responsible for the spontaneous production of anti-DNA in MRL/1 and NZB mice.

Animals↗
PubMed1980

Evidence for abnormalities in separate lymphocyte populations in NZB mice.

Neonatally thymectomized, lethally irradiated NZB X DBA/2 and DBA/2 X NZB F1 mice were reconstituted with NZB or DBA/2 bone marrow cells and NZB or DBA2 thymocytes. Of the four resulting groups of recipient F1 mice, those given NZB bone marrow cells developed high serum IgM levels, irrespective of the thymocyte donor strain. In contrast, recipients of NZB thymocytes were resistant to induction of tolerance to BCG, irrespective of the bone marrow donor strain. Only recipients of NZB bone marrow cells made spontaneous antierythrocyte autoantibodies; of these, the responses of NZB thymocyte recipients were greater and more consistent than those of DBA/2 thymocyte recipients. Recipients of either NZB bone marrow cells or NZB thymocytes made antibody responses to ssDNA; the highest anti-ssDNA responses occurred in recipients of both NZB bone marrow cells and NZB thymocytes. We conclude that functional abnormalities in separate lymphocyte populations underlie different immune abnormalities in NZB mice.

Animals↗
PubMed1979

CBA/N X-linked B-cell defect prevents NZB B-cell hyperactivity in F1 mice.

NZB mice and their F1 hybrids produce excessive polyclonal IgM and autoantibodies of both IgM and IgG classes. CBA/N mice and CBA/N-mothered F1 males fail to make antibody to many T-independent antigens and have low levels of serum IgM; further, these mice lack a population of splenic B cells characterized by a low-to-intermediate density of surface IgM. We have studied male CBA/N, NZB, CBA/N X NZB, NZB X CBA/N, and CBA/J mice; female CBA/N X NZB mice; and males of several control crosses of NZB and CBA/N mice. We have found that the CBA/N X-linked defect of T-independent immune response is completely expressed in CBA/N X NZB mice. In marked contrast to NZB mice and to NZB mice and to NZB F1 hybrids bearing at least one normal X chromosome, the CBA/N X NZB males failed to respond to two T-independent antigens, had small numbers of splenic IgM-producing cells, barely detectable splenic IgM production, and splenic B-cell surface-Ig patterns resembling those of CBA/N mice. These data suggest that the NZB B-cell abnormality resulting in excessive IgM production occurs almost exclusively in that population of B cells affected by the CBA/N X chromome-linked defect. Preliminary studies suggest that CBA/N X chromosome retards the spontaneous development of anti-erythrocyte autoantibodies in CBA/N X NZB males. Castration, known to accelerate autoimmune disease in certain NZB F1 males, appears to have no influence on the immune functions examined in this study.

Animals↗
PubMed1979

Approach to the study of the role of sex hormones in autoimmunity.

Investigators from this laboratory have been studying sex hormones in normal and autoimmune mice for the past 10 years. We have found that immune responses to DNa are influenced by sex hormones. Androgens reduce and estrogens increase both spontaneous and immunization-induced antibodies to single-stranded DNA in NZB X NZW, NZB X C3H, NZB X CBA, NZB X DBA mice. Treatment of female NZB/W mice with testosterone or 5 alpha dihydrotestosterone retards the progress of autoimmunity. Castration is not necessary for this effect. In contrast, danazol has no favorable effect on the disease process. Estrogens cause a marked acceleration of autoimmunity and a reduction in thymus weight. During the course of these studies, we found that a number of problems or variables arise in studying sex hormone effects, including: 1) X-linked genes, 2) metabolism of testosterone to estrogens, 3) dose of hormone, 4) age at which administration is initiated, 5) differential effects of sex hormones on different autoantibodies and various immune responses.

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PubMed1979

IgE mediated triggering of rat basophil leukemia cells: lack of evidence for serine esterase activation.

Inhibition of mediator release from mast cells and basophils by diisopropylfluorophosphate (DFP) and other organophosphorus compounds known to inhibit serine esterases has in the past led to the hypothesis that immunologic triggering of these cells involves an activatable serine esterase. In this study we have shown that two nonphosphorylating or poorly phosphorylating structural analogs of two potent phosphorylators inhibit release of incorporated serotonin from cultured rat basophil leukemia cells. We conclude that, by itself, inhibition of immunologic mast cell triggering by phosphorylating organophosphorus compounds can no longer be considered evidence for involvement of an activatable serine esterase in mast cell triggering.

Animals↗
PubMed1978

Triggering of cultured neoplastic mast cells by antibodies to the receptor for IgE.

Cell surface receptors for IgE were isolated from detergent lysates of iodinated, IgE-saturated, rat basophilic leukemia cells by precipitation with anti-IgE antibodies followed by chromatography at acid pH. The isolated material showed a single 125I-band (m.w. approximately 58,000) on gel electrophoresis in sodium dodecyl sulfate and was used to immunize a rabbit. The resulting anti-serum was reacted with lysates of surface iodinated mouse or rat tumor mast cells. Analysis of the precipitates on (10%) gel electrophoresis revealed one major peak comprising greater than 80% of the detectable counts and having an estimated m.w. of approximately 58,000. The antiserum reacted with detergent-solubilized and cell-bound receptors in the presence or absence of excess IgE; it also inhibited the binding of 125I-IgE. Cultured mouse mastocytoma cells never exposed to IgE released 3H-serotonin when incubated with F(ab')2, but not Fab' fragments of the antiserum, which had been rigorously freed of IgE and anti-IgE. The release was inhibited in the presence of excess IgE, was Ca++ dependent, and equaled 80% of the maximum obtained with IgE and anti-IgE. We conclude that aggregation of the receptors for IgE provides the critical signals for cell activation.

Animals↗
PubMed1977

Dimeric immunoglobulin E serves as a unit signal for mast cell degranulation.

Rat immunoglobulin E (IgE) was treated with a crosslinking reagent, dimethyl suberimidate, and fractionated by gel filtration into monomers, dimers, trimers, and higher polymers. The fractions retained substantial ability to bind specifically to mast cells. About one-third of the cell-bound dimers appeared to bind bivalently. The fractions were assayed in vivo by passive cutaneous anaphylaxis in rats, and for histamine or serotonin release in vitro using normal or tumor mouse mast cells. The monomers showed no activity, while the dimers and higher polymers gave excellent and approximately equivalent responses. We conclude that IgE that has been crosslinked to form dimers prior to the addition to mast cells can serve as a unit signal for triggering IgE-mediated exocytosis.

Animals↗
PubMed1977

Noncytotoxic IgE-mediated release of histamine and serotonin from murine mastocytoma cells.

Cultured murine mastocytoma (AB-CBF1-MCT-1) cells were stimulated to release endogenous or incorporated histamine or serotonin by an IgE-mediated mechanisms without loss of viability. Stimulation was achieved by incubation of the cells with rat IgE-anti-IgE, rat IgE-anti-light chain, fluoresceinated rat IgE-anti-fluorescein, IgE-enriched mouse anti-ovalbumin-ovalbumin, or covalently linked dimers of rat IgE, at doses similar to those optimal for normal peritoneal mast cells. Active cell metabolism and Ca++ were required to obtain release. Despite the latter, no dose of the calcium ionophore, A23187, could be found which caused release without concomitant cytotoxicity. Phosphatidylserine did not enhance release.

Animals↗
PubMed1975

Partial characterization of the cytosol 3 alpha-hydroxysteroid: NAD(P)+oxidoreductase of rat ventral prostate.

The cytosol 3alpha-hydroxysteroid dehydrogenase of rat ventral prostate has been partially purified. The rates of both the oxidation and reduction by crude and partially purified enzymes have been measured with a variety of radioactive substrates, and the effects of several inhibitor steroids have been assessed. Four conclusions have been drawn from the study. First, no detectable 3beta-androstanediol was formed from dihydrotestosterone, and the oxidation of 3beta-androstanediol was undetectable. Second, the cytosol enzyme exhibits a distinct and unique substrate specificity in that steroids with keto or hydroxyl substitution on the 11th carbon of the steroid cannot serve as substrates or as inhibitors of the enzyme. Third, either 5alpha or 5 beta reduction of delta4,3-keto steroids must take place before the steroids can serve as substrates of the enzyme. Fourth, many delta4,3-keto steroids that cannot act as substrates for the enzyme inhibit the enzyme competitively and may well serve as physiological regulators of the reaction in intact cell.

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