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K O Cox

Publications and source records attributed to K O Cox.

At least 37 records · Page 2Linked to original sources
PubMed1983

Experimental erythrocyte autoimmunity prevented by suppressor T cells in mice treated with Cyclosporin-A.

Mice injected with rat erythrocytes produce erythrocyte autoantibodies and suppressor cells that inhibit autoantibody production without inhibiting the net production of antibodies against rat RBC. Here it is shown that injecting mice with Cyclosporin-A daily for up to 13 days during the course of injections of rat RBC significantly inhibits autoantibody production. Antibody production against rat RBC was also inhibited. The Cyclosporin-A-treated mice that did not produce autoantibodies produced suppressor cells that inhibited autoantibody production in adoptive transfer experiments. These suppressor cells, which did not inhibit antibody production against rat RBC, were destroyed by treatment with anti-Thy 1.2 serum and complement. From the results, it is suggested that in this experimentally induced autoimmune disease, suppressor T cells may be activated and/or preferentially spared in Cyclosporin-A-treated mice.

Anemia, Hemolytic, Autoimmune↗
PubMed1983

Effects in mice of rat bromelain-treated RBC and lipopolysaccharide on autoantibody production against bromelain-treated isologous RBC.

Autoantibody production against mouse bromelain-treated (brom) red blood cells (RBC) was significantly increased in mice injected with rat brom RBC. These autoantibodies were not adsorbed by rat brom RBC in serological assays and did not lyse rat brom RBC in plaque-forming cell (PFC) assays using mixtures of rat brom RBC and mouse brom RBC as targets. These data suggest that the increased response induced by rat brom RBC is not due to the presence of common, or similar, antigens on the two types of RBC. The spleens of mice injected with lipopolysaccharide (LPS), or with both LPS and rat brom RBC, had a markedly increased number of PFC lysing mouse brom RBC. About 20% of the PFC induced by LPS and rat brom RBC also lysed rat brom RBC. The autoimmune response was not increased in mice injected twice with rat brom RBC and the secondary response induced by two injections of LPS was lower than that induced by one injection of LPS. However, injection of LPS after an initial challenge with rat brom RBC induced an autoimmune response similar in size to that induced by LPS alone. The decreased secondary response against mouse brom RBC following a second injection of rat brom RBC was associated with decreased production of antibodies of various specificities as detected in a reverse PFC assay. These results do not support the hypothesis that the poor secondary responses against mouse brom RBC following a second injection of rat brom RBC are due to the exhaustive differentiation of autoimmune B cells as part of a fail-safe mechanism to prevent autoimmunity.

Animals↗
PubMed1983

Suppression of autoantibodies is specific for the foreign antigens inducing the autoimmunity.

Mice injected with rat erythrocytes produce erythrocyte autoantibodies and suppressor cells that specifically inhibit the autoimmune response without inhibiting the net production of antibodies against rat erythrocytes. Here it is shown that the suppressor cells bind preferentially to monolayers of rat erythrocytes rather than to erythrocytes from mice or sheep. Suppressor populations depleted of B cells, and cells that adhered to monolayers of rat erythrocytes, lost the ability to suppress the production of autoantibodies in normal mice injected with rat erythrocytes. In contrast, suppressor populations depleted of B cells and cells that adhered to sheep erythrocytes or mouse erythrocytes retained suppressor activity. From these results it is suggested that the regulation of autoantibody production by the suppressor cells in this model may be part of a normal system by which antibody responses to foreign antigens are regulated, and not a unique homeostatic mechanism by which harmful autoimmune responses are eliminated.

Animals↗
PubMed1981

An immunological analysis of the effects of bromelain on the mouse erythrocyte membrane.

The technique of crossed immunoelectrophoresis was used to analyse the effects of bromelain on the antigens contained within the membranes of mouse erythrocytes. Immune sera were obtained from goats that had been injected with membranes prepared from either normal erythrocytes or bromelain-modified erythrocytes. Precipitation patterns obtained by crossed immunoelectrophoresis showed that treatment of erythrocytes with bromelain changed the electrophoretic mobility of a major protein antigen and increased the solubility of two membrane glycoproteins. The possibility that enzymic modification of the erythrocytes led to the creation of entirely new antigenic determinants was not supported by the precipitin patterns obtained using sera absorbed with various membrane preparations.

Animals↗
PubMed1981

Experimental erythrocyte autoimmunity. Specificity of autoantibodies of autoantibody-specific suppressor cells elicited by RBC from various strains of rats.

Autoantibodies and autoantibody-specific suppressor cells are produced in mice injected with RBC from rats. In this report it is shown, first, that the RBC from various strains of rats stimulate similar clones of auto-reactive B-cells. The evidence for this conclusion was obtained using antibodies eluted from the RBC and sera from mice positive in direct Coombs' tests. Autoantibodies elicited by RBC from any strain of rat were absorbed by RBC from all strains of rat tested but not by sheep RBC. Secondly, it is shown that spleen cells from mice injected with RBC of one strain of rat delayed autoantibody production elicited by RBC from syngeneic and allogeneic rats when transferred to syngeneic mice before the first injection of rat RBC. Serum antibody levels to rat RBC were not reduced.

Animals↗
PubMed1981

Suppression of antibody responses by cells from mice treated with picryl sulfonic acid: T cells that suppress IgG antibody without inhibiting concomitant IgE responses.

T cells from mice injected with picryl sulfonic acid (PSA) can inhibit the anti-trinitrophenyl (TNP) antibody responses of mice produced after skin painting with picryl chloride (PCl). This had unusual specificity because the cells could inhibit IgG PFC responses in draining lymph nodes by 90% without affecting anti-TNP IgE responses as measured by heterologous adoptive cutaneous anaphylaxis. Although showing specificity for the class of antibody, the suppressors did inhibit IgG antibody responses to another sensitizer, oxazolone, although to a lesser degree. Responses to TNP-KLH, however, were unaffected.

Anaphylaxis↗
PubMed1980

IgM-autoantibodies against isologous erythrocytes also react with isologous IgG(Fc).

The mechanisms by which the adaptive immune system of animals discriminate between foreign and self components are not known. It is generally believed that antibodies are produced only in response to foreign agents. However, against this axiom there is mounting evidence that normal animals produce autoantibodies against a variety of self components. In two murine model systems, a high proportion of IgM-producing cells secrete autoantibodies. In one model, the autoantibodies are specific for isologous mouse IgG(Fc) and in the other, the autoantibodies are specific for antigens revealed on the surface of mouse erythrocytes (RBC) by proteolytic enzymes. The function of these two autoimmune responses is a mystery. Here we show that the two responses are related. The lysis of mouse RBC, modified with bromelain (brom) by IgM autoantibodies was completely inhibited by isologous IgG(Fc), and antibodies against mouse IgG(Fc) formed precipitin bands with solubilized membranes from mouse RBC. We conclude that mouse RBC membranes and IgG(Fc) have at least one antigenic determinant in common and that this determinant is the target for autoimmune responses in normal mice.

Animals↗
PubMed1980

Experimental erythrocyte autoimmunity. II. Autoantibody-specific suppressor cells present in blood.

Mice injected with rat RBC produce RBC autoantibodies and spleen cells that delay autoantibody production. In this report it is shown that transfer of 5 X 10(6) blood leukocytes from mice producing autoantibodies to syngeneic recipients before the injections of rat RBC were started, significantly delayed autoantibody production. These circulating suppressor cells were effective if transferred up to 3 weeks before the first injection of rat RBC and were destroyed by 2,000 rad of irradiation before transfer.

Animals↗
PubMed1980

Experimental erythrocyte autoimmunity. I. Mice congenic for immunoglobulin allotypes vary in production of autoantibodies but produce suppressor cells not restricted by allotypes.

Erythrocyte autoantibodies can be elicited in mnce by injections of rat RBC which are cross-reactive with mouse RBC. This report shows that induction of autoantibodies is dependent, in part, on gene(s) outside the H-2 complex. Using CBA mice congenic for Ig allotype and the F1 and F2 hybrids, a higher incidence of autoantibody production was observed in mice bearing the Ig allotype 1b (1b/b or 1a/b) in contrast to mice homozygous for the allotype Ig-1a. Serum haemagglutination titres against rat RBC were not reduced in the groups of mice with the lower incidence of autoantibody production. A probable explanation for these observations is that the change in Ig allotype is associated with some change in the variable region determining autoimmune specificity that is governed by VH genes linked to allotype genes. The transfer of 30 x 10(6) spleen cells from Coombs' positive mice to syngeneic recipients before starting the immunization regime with rat RBC suppressed autoantibody production and enhanced antibody production against rat RBC. These suppressor cells were effective in congenic mice and in F1 hybrids, which suggest that the Ig allotype is not a crucial site for the effector stage of suppression of this autoimmune response.

Animals↗
PubMed1979

Impaired regulation of erythrocyte autoantibody production after splenectomy.

C3H mice were given 4 i.p. injections, eac of 2 X 10(8) WAG rat RBC, at weekly intervals. The production of erythrocyte autoantibodies elicited by the cross-reacting rat RBC was assessed using the average direct Coombs' test (DCT) score. Autoantibody production reached higher levels and persisted significantly longer in mice splenectomized 15 days before the first injection of rat RBC. This increased production of autoantibodies was not prevented by injecting each splenectomized mouse i.v. with 5 X 10(7) syngeneic spleen cells immediately after splenectomy. Similarly, splenectomy of mice already DCT+ significantly prolonged autoantibody production which was not prevented by injections of 10(8) cells prepared from the spleens removed at splenectomy. Transfer of spleen cells from mice already DCT+ to mice before the injections of rat RBC were started in the recipients caused a significant reduction in the amount of RBC autoantibodies produced. This suppression of autoantibody production was greater in unsplenectomized mice than in splenectomized mice. The results show that the spleen is involved in the regulation of these erythrocyte autoantibody responses. It is hypothesized that, in addition to the cellular component of the spleen, the splenic architecture and/or environment contributes to the regulation of autoantibody responses.

Animals↗
PubMed1979

In vitro investigation of autoantibody-secreting peritoneal cells and their regulation.

A high proportion of peritoneal cells from untreated mice, after 4--5 days in culture, develop into plaque-forming cells against bromelain-treated mouse red blood cells. The number of plaque-forming cells was increased significantly by exposing the peritoneal cells to ammonium chloride to lyse red blood cells before culture. Conversely, the increase was significantly inhibited by adding before culture untreated or bromelain-treated sheep or mouse red blood cells. Treated or untreated horse or rat red blood cells did not inhibit the increase. Treating peritoneal cells or subpopulations of peritoneal cells with anti-theta serum and complement before culture caused a significant increase in the number of plaque-forming cells against bromelain-treated red blood cells after 3--4 days of culture. Various procedures were used to fractionate peritoneal cells into B-cell enriched and B-cell depleted subpopulations before culture and after culture, to investigate whether some of the plaque-forming cells could be attributed to phagocytic cells. Generally, changes in the number of plaque-forming cells against bromelain-treated mouse red blood cells paralleled changes in B-cells. In some experiments the proportion of plaque-forming cells observed represented up to 85% of the B-cells present. The results suggest that the high level of autoreactivity is due to antibody production by B-cells and that phagocytic cells are not forming spurious plaques. Further, it appears that the autoimmunity is regulated by T-cells and can also be inhibited by mouse RBC.

Animals↗
PubMed1977

Studies of the antigenicity and immunogenicity of bromelain-pretreated red blood cells.

The effects of the proteolytic enzyme bromelain (Br) on the antigenicity and immunogenicity of sheep and mouse red blood cells (RBC) have been investigated. The results presented support the previous claim that there are antigens present on Br RBC that are not present in an exposed form on untreated RBC and that Br RBC have lost some of the antigens present on the surface of normal RBC. The susceptibility of Br RBC to osmotic lysis was very similar to that of normal RBC, implying that the modified RBC were not more fragile than normal RBC. Injection of mice with Br mouse-RBC did not increase the unusually high "background" number of cells producing IgM antibodies against Br mouse-RBC and mice did not mount delayed-type hypersensitivity reactions against Br mouse-RBC, either before or after sensitizing injections of Br mouse-RBC. However, mouse-RBC and Br mouse-RBC elicited similar antibody responses in rabbits and guinea pigs. Although mice appeared unresponsive to Br mouse-RBC injections, delayed-type hypersensitivity responses and antibody production in primary and secondary responses were of similar levels irrespective of whether sheep-RBC or Br sheep-RBC were used as immunogens. From these studies it appears that mice have B-cells producing antibodies against the "new" antigens on Br mouse-RBC, but there are no T-cells that respond to these antigens by way of "helper" activity in antibody production or by way of cell-mediated immune reactions.

Animals↗
PubMed1977

Disappearance of IgG2B autoantibodies associated with recovery from anaemia.

Mice immunized with cross-reacting rat erythrocytes develop autoimmune haemolytic anaemia as indicated by haematological data and erythrocyte autoantibodies. With continued immunization the mice recover haematologically but remain Coombs' positive. Coombs' tests were performed using monospecific antisera to determine whether the recovery from anaemia was associated with a change in the class or subclass of the autoantibodies produced. In both splenectomized mice and in unsplenectomized mice the following subclass of erythrocyte autoantibodies were present: IgG1, IgG2A, IgG2B. IgA autoantibodies were not detected and IgM autoantibodies were only detected in splenectomized mice 1-3 weeks after the IgG autoantibodies had appeared. After six immunizations the frequency of IgG2B autoantibodies decreased and by the tenth immunization and thereon, IgG2B autoantibodies were not detected. It is proposed from these results that the anaemia is caused by IgG2B autoantibodies and the the sudden exacerbation in the anaemia that occurs in splenectomized mice is due to the production of IgM autoantibodies.

Anemia, Hemolytic, Autoimmune↗
PubMed1975

Inhibition of migration of murine spleen cells by Rauscher leukemia virus-infected syngeneic cells.

The in vitro migration of spleen cells from BALB/c mice infected with Rauscher leukemia virus (RLV) was markedly inhibited 10 days after RLV inoculation. Mixtures of infected and uninfected spleen cells used in the ratio of 1:4 in an effector-cell/indicator-cell system showed that viable RLV-infected spleen cells could inhibit the migration of uninfected spleen cells in a manner indistinguishable from that mediated by sensitized spleen cell reacting to specific antigen.

Animals↗