Nonspecific suppressor elements in murine allogeneic radiation chimeras.
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Biomedical subjects
Publications and source records attributed to N Gengozian.
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Saguinus fuscicollis ssp., S.o. oedipus, and S. nigricollis marmosets were immunized with white blood cells (WBC) from S.f. illigeri marmosets. Of the three genetic donor-host combinations attempted, only an interspecies immunization of S.o oedipus marmosets resulted in antibody formation which was detectable by agglutination or cytotoxicity tests. Analysis of one of the antisera with a panel of WBC from S.f. illigeri marmosets indicated varying specificities, reactions ranging from strong, intermediate, to completely negative. That the serum was detecting genotypic as well as phenotypic markers was suggested by the similarity of reactions of WBC from co-twin pairs and in preliminary testing of individual families.
Reactivation of fetal hemoglobin gene expressions was studied in new-world monkeys (marmosets). After a series of intraperitoneal injections of D-thyroxine, fetal hemoglobin production was increased in three experimental animals. Control animals were unaffected by the injection of the solvent. Because the percentage of cells containing fetal hemoglobin exceeded the total percentage of fetal hemoglobin, it was concluded that thyroid hormone influenced the synthesis of fetal hemoglobin rather than the development of a population of fetal cells.
This study deals with the comparative effects of gamma irradiation on T and B lymphocytes in mice. Quantitatively, splenic T cells appeared substantially more radioresistant than B cells. However, in the thymus, the mesenteric lymph node and peripheral blood, both cell types were highly radiosensitive. No repair processes could be detected with respect to lymphocyte killing, since reducing the dose rate or fractionating the dose resulted in no reduction in cell destruction. Splenic B cells which remained intact 3 days after doses of 600 R or larger were impaired in their ability to form caps, whereas T cells capped normally. Spleen cells which were viable 3 days after irradiation bore latent radiation damage which was manifested as a reduced ability to survive and generate plaque-forming cells in vitro. Attempts to separately assess irradiated T and B cell immunocompetence in vitro suggested that at doses of 300 R and below, surviving B cells were more impaired than T cells. After a 600 R dose, neither cell type appeared to be functional.
Cross-reactivity between marmoset, chimpanzee, human and pig zona pellucida antigens was demonstrated by immunofluorescence and zona precipitation. In marmosets, anti-zona antibody prevented sperm attachment to eggs in vitro, and the antibody could be detected on zonae of ovarian oocytes following passive immunization. Use of the marmoset as an animal model in testing feasibility of the zona approach to immunocontraception is discussed.
A comparison of the in vivo and in vitro antibody response capabilities of two marmoset species, Saguinus fuscicollis and Saguinus oedipus oedipus, revealed the former to be superior in elaborating humoral antibody. In vivo challenges with Escherichia coli lipopolysaccharide (LPS) and Salmonella typhi flagella consistently yielded higher antibody titres in S. fuscicollis; indeed, with LPS antigen, multiple inoculations of S.o. oedipus marmosets led ultimately to a decrease in antibody formation, in contrast to the anamnestic response of S. fuscicollis. This species differential in immune competence was also suggested in the in vitro stimulation of peripheral blood leucocytes (PBL) and spleen cells with sheep red blood cells (RBC). None of 55 S.o. oedipus PBL cultures and 49 of 89 (55%) S. fuscicollis cultures responded to the test antigen. A similar differential in response to sheep RBC was noted with the spleen cells of each species, although this report contrasts the antibody-forming potential of two marmoset species, a comparison of the immunological response profile of marmosets to those of other laboratory animals challenged with similar antigens suggests these primates may be relatively incompetent. The possible relationship between the haemopoietic chimerism of marmosets and a diminished immune competence is discussed.
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We find that colonic adenocarcinoma, which is an extremely rare neoplasm of all animals except man and carcinogen-treated rodents, occurs spontaneously in some marmosets. The cotton-topped Saguinus oedipus oedipus is particularly prone to develop it, but we have found it also at necropsy in Callimico goeldii (Goeldi's marmoset). Numerous metastases to regional lymph nodes develop. The cancers arise de novo in the mucosa and early invade the submucosa and lymphatic apparatus and paracolonic lymph nodes. These findings and the continuing occurrence of this cancer in our colony suggests that the marmoset may be the long-sought primate model for experimental intestinal carcinogenesis.
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Marmosets are natural blood chimeras, this condition resulting from the high frequency of fraternal twinning and the consistent development of placental vasular anastomoses between the two embryos. Identification of chimerism by sex-chromosome analysis of cultured blood lymphocytes provided a means of determining the proportion of chimerism among T and B lymphocytes. Peripheral blood lymphocytes were enriched for T or B cells by filtration through a nylon column (yields greater than 95 per cent T-cells) or inactivation of T lymphocytes by treatment with a goat anti-marmoset thymocyte antiserum in the presence of complement (yeilds greater than 95 per cent B cells). Mitogenic stimulation of these separated, enriched cell populations yielded metaphase plates which could be scored for percentage male and female cells. Tests on five different blood chimeras showed the T- and B-lymphocyte chimerism to be the same. Stimulation of blood lymphocytes with cells from another species of marmoset in a mixed lymphocyte culture test revealed the chimeric T-cell response (i.e., host and co-twin cells) to be similar to that obtained with a mitogenic lectin. The demonstration of equivalent T- and B-cell chimerism in these animals suggests derivation of these cells from a common stem cell pool and the response of both T-cell populations to an antigenic stimulus in proportions similar to their percentage chimerism suggests complete immunologic tolerance exists in this species for co-twin histocompatibility antigens.
The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production.
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Bone marrow cells from adult and abortus primates (marmosets) were incubated in vitro to determine their responsiveness to L-thyroxine. 3H-leucine incorporation into purified globin chains was the parameter assayed to determine responsiveness. Bone marrow from spontaneously aborted animals consistently was stimulated by the presence of physiologic levels of L-thyroxine. Bone marrow cells from adult animals were unaffected by the hormone.
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The immune competence of two species of marmosets, S. fusciollis and S. oedipus, was evaluated by the intravenous (i.v.) and intramuscular (i.m.) injection of sheep red blood cells (SRBC). In S. fusciollis marmosets, 1 ml of a 50% suspension yielded titres of haemolysin and agglutinating antibodies equal to or greater than 1 ml of a 10% dose of antigen. In both species, the i.v. route, while resulting in formation of 19S and 7S agglutinins, yielded only 19S haemolysins, even after multiple antigen injections. Repeated i.v. injections resulted in a progressive decrease in peak titres, in contrast to the i.m. route, where booster inoculations gave a typical anamnestic response. Jerne plaque-forming cells (PFC) in the spleens of S. oedipus marmosets showed predominately 19S plaques after a primary i.v. challenge; only 19S PFC were detected in the spleen of an animal that had been given multiple inoculations, the type of antibody produced reflecting that found in the serum. 19S but not 7S haemolysins of both species were sensitive to heating at 56 degrees C for 1/2 hr. The serum titres and splenic PFC data from the marmosets suggest these animals, particularly S. oedipus, respond poorly to SRBC when a comparison is made to similar studies in mice and rats.