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Treatment of NZB/W F1 mice with NZW splenic T cells or with serum of mice experiencing the graft-versus-host reaction: suppression of ongoing anti-double-stranded (ds) DNA antibody formation and improvement of renal function.

Seven-month-old NZB/W F1 mice were inoculated with 5 X 10(7) NZW spleen cells. The mice so treated showed a clear fall of anti-double-stranded (ds) DNA antibody titers accompanied by a decrease in blood urea nitrogen (BUN) concentration. Mice so treated showed markedly increased survival times (more than 17 months) compared with untreated controls (mean +/- SD 8.38 +/- 0.75 months). A cell fractionation study suggested that T cells among NZW spleen cells play a major role. Recipients of the unfractionated or the T-cell fraction of NZW spleen cells had histologically less glomerulonephritis than untreated control NZB/W F1 mice. NZW B-cell transfer to NZB/W F1 mice had no effect. Serum obtained from NZB/W F1 mice receiving NZW spleen cells 10 days previously (graft-vs-host (GVHR) serum) was injected into 8-month-old NZB/W F1 mice. A clear fall in anti-ds DNA antibody titers and inhibition of age-associated sharp increases in BUN were observed. The mean life span of these mice (10.50 +/- 0.58 months) was significantly longer than that of untreated controls (8.69 +/- 0.38 months). GVHR serum had the ability to suppress anti-ds DNA antibody formation by NZB/W F1 spleen cells in vitro. Allogeneic GVHR serum prepared in C57B1/6 X DBA/2 (BDF1) mice by transferring C57B1/6 spleen cells was also effective in suppressing anti-ds DNA antibody formation in vitro.

Animals↗

Induction of suppressor T cells of antibody formation under conditions that preferentially stimulate DTH.

These studies describe the conditions under which antibody-forming cells and TDTH cells are selectively induced in vitro. TDTH cells are preferentially stimulated when high doses of antigen are included in the culture. Antibody-forming cells, on the other hand, are optimally stimulated with a 100 to 1000-fold less concentration of antigen. The conditions that optimally stimulate TDTH cells also induce a population of suppressor T cells that inhibit the antibody response. However, although their inductive requirements are similar, the suppressor T cells of antibody formation are a distinct subpopulation of cells from the TDTH cells. Whereas the suppressor T cells are LY-1-, 2+, 4-, 6+, and Ia+; the TDTH cells are Ly-1+, 2+/-, 4-, 6+, and Ia-. Furthermore, the DTH cells are sensitive to high doses of irradiation, whereas the suppressor cells are resistant. Based on the Ly phenotype and the kinetics of suppression, the suppressor T cells are not the "feedback suppressors" that have been identified in other systems. The system described in this paper provides a means whereby the cells that regulate humoral and CMI can be studied in vitro.

Animals↗

Relationship of major histocompatibility complex class II genes to inhibitor antibody formation in hemophilia A.

Approximately 14% of transfused hemophiliacs develop an anti-factor VIII inhibitory antibody which specifically neutralizes factor VIII procoagulant activity. In this study an association of the major histocompatibility complex (MHC) with inhibitor antibody formation was evaluated by restriction fragment length polymorphism (RFLP) analysis using BamHI, EcoRI, HindIII, PstI, PvuII and TaqI digested genomic DNA probed with DP beta, DQ alpha, DQ beta and DR beta class II MHC gene probes. The RFLP patterns for 16 non-inhibitor and 11 inhibitor hemophiliac patients were analyzed. These 24 enzyme:probe combinations generated 231 fragments. Fifteen (15) fragments associated with the inhibitor phenotype; odds ratios ranged from 5.1 to 45 and lower bounds of 95% confidence intervals were greater than 1.000 for all 15 fragments. Five (5) fragments associated with non-inhibitors, with odds ratios ranging from 6.4 to 51.7. This report establishes a MHC related genetic basis for the inhibitor phenotype. No statistically significant differences in the distribution of serologically defined HLA-DR phenotypes were observed between the inhibitor and non-inhibitor groups.

Adsorption↗

[Insulin antibody formation in diabetic children (author's transl)].

This is a report about the findings of insulin antibody formation (circulating IgG-antibodies) in 18 diabetic children. 1. High levels of antibodies during treatment with conventional insulin show a remarkable decrease under treatment with highly-purified insulins. 2. Insulin binding capacities were also found in children treated from diagnosis of the disease with highly-purified insulins, but they were all below 1.0 mU/ml. 3. Infectious diseases and intermittent insulin application seem to provoke an, at least briefly, increase of antibodies. 4. High levels of antibodies cause a high insulin requirement. Therefore only highly-purified insulin should be used for the treatment of childhood onset diabetes mellitus.

Antibodies↗

Adjuvant action of bacterial endotoxin and colchicine on antibody formation in the hamster.

Endotoxin was demonstrated not to act as an adjuvant in the primary antibody response in the Syrian hamster. Minimal adjuvant action was demonstrable in antibody formation to a second injection of bovine gamma globulin. The immunological status of the hamster towards the endotoxin did not alter this weak adjuvant action. It was confirmed that the antimitotic drug colchicine will act as an adjuvant in the primary antibody response to sheep red blood cells but not to bovine gamma globulin or endotoxin in the Syrian hamster.

Adjuvants, Immunologic↗

[Age-related changes in the immune response of (CBA X C57BL)F1 hybrid mice. I. Stimulation of antibody formation in old animals].

A study of immune response to sheep erythrocytes in CBA X C57BL F1 hybrids of different age has shown a sharp fall in the number of antibody forming cells in the spleen of old mice. An analysis of data on stimulatory effect of preliminary sublethal irradiation and introduction of hydrocortisone upon antibody formation in old mice allows to conclude that cells-regulators inhibiting the antibody forming cells are accumulated in the spleen of old animals. These cells are sensitive to ionizing irradiation and hydrocortisone.

Aging↗

Chondroitin sulfates used as adjuvants for antibody formation and as mitogens for B cells.

The effects of chondroitin sulfates (ChS) A and C on antibody formation in mice and chickens and on proliferation of murine B cells in vitro were determined. Simultaneous injection of ChS with sheep erythrocytes (SRBC) caused enhanced antibody production as measured by plaque-forming cells per spleen on day 5 after antigen and by serum agglutinin titers. ChS.C was more active than ChS.A and intravenous (i.v.) injection was far more effective, requiring 100-fold lower doses, than intraperitoneal (i.p.) injection. Responses of chickens could be enhanced by i.v., but not by i.p., injection of ChS.C with SRBC. Simultaneous injection of ChS.C with trinitrophenylated Ficoll had no effect, but injection of ChS.C 2 days after this antigen significantly increased the responses. Although ChS.C and ChS.A both caused proliferation of normal and athymic mouse spleen cells, the concentrations required for this effect in vitro were much higher than those needed for the in vivo effect. ChS.C caused only a slight increase in delayed hypersensitivity to a contact sensitizer.

Animals↗

Further evidence against random polyclonal antibody formation in mice with lupus-like graft-vs-host disease.

The pathologic symptoms in F1 mice with chronic graft-vs-host disease (GVHD) (GVH F1) strongly resemble those of systemic lupus erythematosus (SLE). Mice with SLE-like GVHD do not produce antibodies to a number of non-self and self antigens. This finding is inconsistent with the widely accepted view that the (auto)-antibody formation in SLE is polyclonal in the sense that B cells are triggered at random, i.e., irrespective of their specificity. In the present study, therefore, we performed a systematic study of the kinetics of total IgM- and IgG-secreting splenic B cells and tested their specificities. The total IgM-secreting B cell population was increased only in the first week after the initiation of SLE-like GVHD; it seemed to reflect a random, but self-limited, polyclonal B cell stimulation. In contrast, the total number of IgG-secreting cells in the GVH F1 mice was increased to a much higher extent than that of the IgM-secreting cells and remained increased. At no time during GVHD was there an increase in the number of plaque-forming cells (PFC) spontaneously secreting IgG antibodies to non-self antigens. The GVH reaction (GVHR) did, however, lead to the appearance of PFC that secreted IgG antibodies to DNA. Similarly, the GVH F1 mice showed high serum titers of antibodies to self antigens characteristic of SLE and to endogenous viruses, but during the entire observation period they failed to develop serum antibodies to non-self antigens and insulin. Hence, the enhanced production of Ig, especially that of IgG, that occurs in SLE-like GVHD is not a random process, because it requires the presence of antigen, or signal 1. The data support our hypothesis that only certain kinds of self antigen, such as DNA and cell membrane epitopes, can cross-link the Ig receptors on the corresponding B cells and thus provide an adequate signal 1. Given the increase in help, or signal 2, in chronic GVHD, only the B cell clones that simultaneously receive an adequate signal 1 seem to be driven into clonal proliferation and IgG secretion.

Animals↗

Inhibition of IgE antibody formation by plasmid DNA immunization is mediated by both CD4+ and CD8+ T cells.

BACKGROUND: We previously showed that immunization of mice with plasmid DNA (pDNA) encoding the Escherichia coli beta-galactosidase gene (pCMV-LacZ) induces a Th1 response, whereas beta-galactosidase (beta-gal) in saline or alum induces a Th2 response. Furthermore, the Th1 response dominates over the Th2 response and downregulates preexisiting IgE antibody formation. Here, we determined by passive transfer of CD4+ or CD8+ lymphocytes and by immunizing beta2-microglobulin knockout (beta2-M KO) mice whether CD4+ and/or CD8+ cells from pDNA-immunized mice suppress IgE antibody production. METHODS: BALB/c mice were injected with either CD4+ or CD8+ lymphocytes from naive beta-gal-in-alum or pCMV-LacZ-immunized mice, then immunized with beta-gal in alum, and the IgE antibody formation was determined. Second, C57BL/6 wild-type (WT) or beta2-M KO mice were immunized with beta-gal orpCMV-LacZ, and the IgE antibody production was assessed. RESULTS: Passive transfer of both CD4+ and CD8+ lymphocytes from pDNA-immunized mice suppressed the IgE antibody response by 90% compared to transfer of CD4+ T cells from naive or beta-galin-alum immunized mice. beta2-M KO mice produced 3 times more IgE than the WT control mice both in the primary and secondary response. CONCLUSION: Both CD4+ and CD8+ subsets of T cells from pDNA-immunized mice can suppress IgE antibody production by affecting the primary response and/or by propagating the Th1 memory response in a passive cell transfer system. Immunization with pDNA-encoding allergens may be an effective new form of immunotherapy for atopic diseases.

Animals↗

[Effect of starch-induced structural and functional modification in a population of free phagocytes on antibody formation induction by ram erythrocytes in mice].

The influence of the starch-induced modification of the population of free phagocytes on the induction of antibody formation by sheep red blood cells (SRBC) in mice has been studied. The intraperitoneal injection of starch has been shown to render a pronounced modulating effect on immune response stimulated by the intramuscular injection of the antigen. The injection of a small dose of SRBC into the abdominal cavity enriched with starch-stimulated monocytes is accompanied by an increase in immune response; this phenomenon is not observed after immunization with a large dose of the antigen. Starch-stimulated macrophages, when introduced with SRBC into syngeneic recipients, show stimulating influence on immune response.

Animals↗