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Biomedical subjects

T G Wegmann

Publications and source records attributed to T G Wegmann.

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

Vaccination against spontaneous abortion in mice.

We report here that the high rate of spontaneous resorption observed in CBA/J female mice mated with DBA/2 J males can be dramatically reduced by vaccination with Balb/c male spleen cells, but not by CBA/J or DBA/2 J male spleen cells. This effect correlates with the differential ability of Balb/c spleen cells to induce MLR suppressor activity in CBA/J female mice, and should lead to a better understanding of the immunology of the materno-fetal relationship.

Abortion, Habitual↗
PubMed1983

Primary structures of human alpha-fetoprotein and its mRNA.

DNA complementary to human alpha-fetoprotein (AFP)mRNA was cloned in the plasmid pBR322. Analysis of three overlapping cDNA clones revealed most of the nucleotide sequence of AFP mRNA, and the remaining nucleotides at the 5' end of the mRNA were elucidated from a cloned genomic DNA fragment. The amino acid sequence was deduced from the nucleotide sequence, which revealed 19 amino acids in the signal sequence and 590 amino acids in mature AFP. There are 15 regularly spaced disulfide bridges, which generate a folding structure having three repeating domains. There is one potential N-glycosylation site, Asn-Phe-Thr, in the amino acid sequence. In comparison with mouse AFP, 66% of the amino acid sequence was conserved, with the highest identity (72%) in domain 3, followed by domain 2 (67%) and domain 1 (59%). In comparison with human albumin, a 39% conservation of primary structure was found. Again, the similarity was the highest in domain 3 and the lowest in domain 1. Human AFP and human albumin are similar in overall structure, but certain parts of the molecules differ significantly in their predicted secondary structure.

Amino Acid Sequence↗
PubMed1982

Tolerance and autoimmunity to erythroid differentiation (B-G) major histocompatibility complex alloantigens of the chicken.

Hematopoietic chimeras were produced at four different stages of ontogeny between two allogeneic strains of chickens. All chimeras produced by parabiosis at day 12 of embryogenesis and the majority (83%) of the ones produced at day 15 by intravenous injection of allogeneic stem cells remained healthy, chimeric, and specifically tolerant at both the humoral and cell-mediated level throughout a long examination period. Chimeras generated at day 17 of embryogenesis demonstrated specific unresponsiveness at the cell-mediated level but produced specific anti-donor alloantibodies directed against erythrocyte-associated major histocompatibility complex (MHC) (B-G) antigens. These chimeras and a minority (17%) of the chimeras generated at day 15 of embryogenesis developed severe antibody-mediated autoimmune hemolytic anemia after the 5th mo of age and succumbed to massive bursal lymphomas and metastases by the 10th mo of age. The immunological and pathological characteristics of these birds appear to reflect an autoimmune state rather than one of tolerance. Erythroid chimeras generated at day 21 of ontogenic development displayed normal levels of GVH reactivity. These birds were eventually able to eliminate the chimeric state and remained healthy until deliberately killed. These results show that there is a critical period in embryogenesis during which the induction of allogeneic erythrocytic chimerism leads to the development, in adult life, of severe autoimmune anemia, B cell lymphomas, and death. B-G MHC antigens are erythroid differentiation antigens of the chicken. Polymorphic determinants on B-G antigens appear to be important cross-reactive determinants (with environmental bacteria), against which a high background immunity exists. Evidence is presented that the immune response to B-G antigens is responsible for the development of autoimmunity and other pathological events that follow and that tolerance to class I MHC antigens (B-F antigens) shared by lymphocytes erythrocytes is maintained at the same time that B-G tolerance is broken.

Anemia, Hemolytic↗
PubMed1982

Characterization and cross-reactivity of human and mouse oncofetal antigens. Use of a new solid phase assay for detection of cell surface antigens.

Oncofetal (OF) antigens have been isolated from mouse F9 teratocarcinoma cells, mouse testicular cells, and human molar tissue by detergent extraction followed by dialysis. The soluble antigens have been used in solid phase radioimmunoassay (SPRIA) and enzyme-linked immunosorbent (ELISA) assay. Specific antibodies have been raised to these antigens in mice. By using these antisera, extensive cross-reactivity was found between mouse and human OF antigens. A human trophoblastic tumor cell line BEWO absorbed out mouse anti-F9 reactivity. Patients with tumors of germinal origin were found to have antibodies which cross-react with mouse and human OF antigens. This new assay is a rapid and sensitive method for the screening of monoclonal antibodies against these antigens as well as for detecting antibodies to tumors bearing these antigens in patients.

Absorption↗
PubMed1982

Alphafetoprotein messenger RNA in human embryonal carcinoma grown in nude mice, and cloning of its complementary DNA.

Messenger RNA for human apha-fetoprotein (AFP) was partially purified from human testicular embryonal carcinoma grown in nude mice. DNA complementary to the mRNA was synthesized, tailed with oligo(dC) and inserted at the PstI site of the plasmid pBR322 tailed with oligo(dG). Escherichia coli strain LE392 was transformed with the chimeric plasmid and colonies were screened for human AFP mRNA sequences by hybridization with DNA complementary to mouse AFP mRNA (greater than 95% pure). Five colonies showed positive hybridization. The plasmid pHAF2, containing the largest insert, 900 nucleotides, was further characterized by hybrid-arrest of translation of AFP mRNA, restriction endonuclease mapping and partial nucleotide sequence analysis. It was found that the AFP complementary DNA (cDNA) sequence in pHAF2 corresponded to the 3'-end of AFP messenger RNA (mRNA), and showed a restriction map entirely different from that of mouse AFP cDNA clones previously reported.

Animals↗
PubMed1981

Is acquired immunological tolerance genetically transmissible?

We have attempted to verify that acquired characteristics can be transmitted through the male germ line by using as a model system the vertical transmission of specific immunological tolerance to major histocompatibility antigens. Tolerant males were a tetraparental mouse and separated parabionts, in each case showing stable lymphoid chimerism. Tolerance in the progeny was assessed by two in vivo assays, rejection of cardiac allografts and clearance of 131I-labeled tumor cells. We were unable to find evidence for heritability of the tolerant state in tetraparental or parabiont males, with either assay system.

Animals↗
PubMed1981

The ontogeny and turnover kinetics of paternal H-2K antigenic determinants on the allogeneic murine placenta.

In previous reports we provided evidence for the expression of paternal H-2Kk antigens on the placenta, accessible to maternal circulation. We have now examined the ontogeny of paternal H-2Kk antigens in the placenta from day 10 to day 17 of gestation and find a steady increase per gram placenta. In order to substantiate the proposal that the placenta functions as an immunoabsorbent barrier preventing the entry of anti-paternal antibodies to the fetus, we monitored the uptake of monoclonal anti-paternal H-2Kk antibody by target (antigen-bearing) and control fetuses and placentas at various intervals after injection. We have previously shown that F(ab')2 anti-H-2Kk behaves like intact immunoglobulin in placental immunoabsorption studies, and demonstrate here that the peak placental uptake of the antibody is not affected by the removal of the Fc portion, whereas its rate of clearance is increased. In contrast to the anti-H-2Kk antibody, monoclonal anti-I-Ak (specificity 17) antibody (IgG2a) shows no placental immunoabsorption.

Animals↗
PubMed1980

Why didn't your mother reject you?

There are two mechanisms by which the fetus escapes damage from the maternal immune response during pregnancy. First, the placenta serves as an antigen-bearing immunoabsorbent barrier between the maternal and fetal circulation, so that the mother's humoral immune response to fetal antigens derived from the paternal major histocompatibility complex has no effect on the fetus. Second, the placenta serves as a physical barrier to the entry of maternal antifetal lymphocytes and thus prevents the maternal cell-mediated immune response from harming the fetus. Evidence supporting these two mechanisms is presented in this paper.

Animals↗
PubMed1980

Models for the production of stable hematopoietic chimerism across major histocompatibility barriers in adults.

Experiments presented in this paper indicate that DBA/2J (H-2d) mice parabiosed for more than 100 days to the F1 hybrid between DBA/2J and C3H/HeJ (H-2k) contain in their serum an anti-H-2k antibody that is preferentially reactive with hematopoietic tissue and is also capable of killing C3H/HeJ colony-forming stem cells in vivo (CFU-S). These findings make the antibody a likely participant in the "takeover" reaction, in which DBA/2J red and white cells eventually replace the F1 hybrid blood system. With these observations used as a basis, 10(8) DBA/2J spleen cells were injected along with anti-H-2Kk (anti-host) monoclonal antibody into 10-wk-old (DBA/2J x C3H/HeJ)F1 hybrid hosts. The recipients had a high surivival rate and exhibited long-term chimerism. Unlike the situation in the parabionts, the DBA/2J lymphoid cells in the injection chimeras were found to be unresponsive to C3H/HeJ alloantigens. This could result from the continued presence of F1 hybrid stimulator cells, which are missing in the parabionts. The injection chimeras indicate that one can establish stable chimerism in adult mice without irradiation or metabolic poisoning.

Absorption↗
PubMed1979

Tolerance induction during ontogeny. I. Presence of active suppression in mice rendered tolerant to human gamma-globulin in utero correlates with the breakdown of the tolerant state.

A specific state of T- and B-cell tolerance to human gamma-globulin (HGG) was induced in utero by intravenous administration of the deaggregated antigen to pregnant BALB/cCr mice. Tolerance persisted in the offspring until the 12th-wk of age and then began to gradually disappear. Suppressor cells could only be found when responsiveness to HGG ultimately appeared in the in utero-treated animals but not when they were completely unresponsives. In contrast, HGG-specific suppressors found in animals made unresponsive to HGG as adults appear to be associated with either the establishment and/or maintenance of the unresponsive state. To the extent that these experiments are consistent with natural self-tolerance to a serum protein, we conclude that active suppression is not a prerequisite from maintenance of unresponsiveness to self.

Animals↗
PubMed1979

Pregnant mice are not primed but can be primed to fetal alloantigens.

In this report we present evidence gathered from various stages of murine pregnancy that indicates that pregnant females have no demonstrable immune effector function directed against their semiallogeneic fetuses. Specifically, by using in vitro assays we found that cytotoxic lymphocytes were not present in pregnant mice, and pregnant mice challenged with radiolabeled paternal strain leukemia cells showed no evidence of immune elimination. Nonetheless, immunity measurable both in vitro and in vivo was readily induced by priming with the paternal strain cells. No harm to the fetus was observed in primed mothers. These results cast doubt on the relevance of mechanisms proposed that involve systemic active suppression during pregnancy. The results are compatible with the hypothesis that the placenta acts as a barrier, preventing fetal cells from priming the mother.

Animals↗