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T G Wegmann

Publications and source records attributed to T G Wegmann.

At least 91 records · Page 5Linked to original sources

The ability of the murine placenta to absorb monoclonal anti-fetal H-2K antibody from the maternal circulation.

In previous work we have found that partially purified 125I-labeled anti H-2 antibody is localized in the placenta when injected i.v. into females pregnant by males bearing the target haplotype. This led to the concept that the placenta is an H-2 antigen-bearing immunoabsorbent barrier between mother and fetus. In this report we have used an anti-H-2Kk monoclonal antibody of the IgG2a subclass, also labeled with 125I, to verify this concept, as well as to improve the genetic definition of the immunoabsorbent antigen. In addition we have prepared F(ab')2 fragments of this antibody, and these also show the immunoabsorbent effect. This indicates that transport into fetally derived tissues via Fc binding is not a prerequisite for reaction of the antibody with paternal strain H-2 K antigens.

Absorption↗

Allogeneic placenta is a paternal strain antigen immunoabsorbent.

A partially purified 125I-labeled antibody directed against the murine major histocompatibility complex and injected i.v. pregnant females is selectively absorbed by the placenta when the fetus bears the appropriate targen antigen. The placenta specifically absorbs the antibody at both 13 days and 17 days of gestation, and the differential uptake is found as early as 2 hr after injection and as late as 12 hr. It is also seen in 13-day placentas that have had the fetus removed surgically, indicating that fetal circulation is not essential for the absorption to take place. Specificity controls eliminate the possibility that the differential uptake is due to Fc receptor binding or undefined effects of hybrid vigor. This increase in binding is not seen in the livers, spleens, kidneys, or lungs of the pregnant females. There is a slight decrease in radioactivity in the serum. These results indicate that the placenta is a paternal antigen-bearing immunoabsorbent that could serve as a barrier between the maternal immune response and the semi-allogeneic fetus.

Absorption↗

Allogeneic pregnancy as immunoabsorbent.

Experiments in the past have indicated that both human and rodent females undergo immune recognition of paternally derived antigens during pregnancy. Although the mechanisms that allow pregnancy to proceed in the face of this process have not yet been clarified, one simple possibility is that the paternal strain antigens are presented in a manner capable of neutralizing the maternal immune response. This predicts that allogeneically pregnant females should be capable of neutralizing passively administered cytotoxic anti-paternal strain antibody, with no consequent harm to the fetus. In this paper we demonstrate by two different methods that allogeneically pregnant mice rapidly absorb passively administered antibody directed against paternal strain major histocompatibility (H-2) antigens when compared to control mice pregnant by syngeneic or third party males. The possible sites where this absorption occurs are discussed.

Animals↗

The genetics of tolerance induction in histoincompatible parabiosed mice.

The effect of varying the H-2 complex on the survival of parabiosed mice was investigated using a strain combination known to lead to about 50% long-term survival. While 45.6% of DBA/2J (H-2d) with (DBA/2J x C3H/HeJ)F1 (H-2d/H-2k) parabionts survive to 100 days or more, 69% of DBA/2J with (DBA/2J x C3H.NBSn)F1s (H-2d/H-2p) survive that long; only 16% of DBA/2J with (DBA/2Jx C3H.SWSn)F1s (H-2d/H-2b) survive to 100 days. The plot of hematocrits as a function of time after parabiosis differs significantly between the 45.6% surviving strain combination (which shows the classical pattern of parental polycythemia and F1 hybrid anemia) and the 69% surviving strain combination (which shows no divergence in parental and F1 hematocrit values). Furthermore, the 69% surviving strain combination often (5/14) persists in a chimeric state as judgec by starch gel electrophoresis of rec blood cell lysates; the other two strain combinations show no demonstrable red cell chimerism. The conclusion is suggested that the mechann these two generally successful strain combinations tested, and appears to be a function of the H-2types of the partners.

Animals↗

Immunological tolerance. Dissociation between in vivo and in vitro reactivity in parabiosed mice.

Although most mouse strain combinations succumb to a lethal wasting disease when parabiosed across a strong histocompatibility (H-2) barrier, a high proportion of DBA mice parabiosed to DBA/C3H F(1) hybrids survive and appear healthy. DBA mice accept C3H skin grafts following parabiosis, and may therefore be considered operationally tolerant of C3H antigens. Nonetheless, spleen cells from long-term DBA and F(1) parabionts give normal and enhanced responses, respectively, to C3H antigens in mixed lymphocyte culture (MLC). This indicates that the tolerance mechanism can distinguish between MLC recognition reactivity and in vivo effector reactivity, and that the former can therefore exist in the absence of the latter.

Animals↗

Active suppression as a possible mechanism of tolerance in tetraparental mice.

Previous work has indicated that tetraparental mice, chimeric since the eight-cell stage because of embryo fusion using histoincompatible strain combinations, possess autospecific immune cells and blocking antibodies. Although this phenomenon has been demonstrated in vitro, it may have relevance to the self-tolerance shown by these mice in vivo. The experiments described here indicate that spleen cells from tetraparental mice can block mixed lymphocyte reactions between the two parental cell types, but not between unrelated strains. Furthermore, this suppressive ability is not affected by an otherwise effective treatment of the tetraparental spleen cells with anti-theta antibody and complement. The in vitro experimental system elaborated here should help to characterize the cell type responsible for the suppression.

Animals↗