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Biomedical subjects

R Korngold

Publications and source records attributed to R Korngold.

95 records · Page 6Linked to original sources
PubMed1980

Negative selection of T cells causing lethal graft-versus-host disease across minor histocompatibility barriers. Role of the H-2 complex.

With a model in which CBA T cells cause lethal graft-versus-host disease (GVHD) in irradiated B10.BR mice (H-2-compatible mice that express multiple minor histocompatibility antigen [HA] differences), information was sought on whether the induction phase of GVHD to minor HA is H-2 restricted. When unprimed CBA (H-2k) T cells were recirculated from blood to lymph for 1 d through irradiated H-2-compatible B10.BR or B10.K mice, the T cells underwent specific negative selection to the minor HA of the host, i.e, the filtered T cells failed to cause GVHD after transfer to B10.BR mice. With filtration through totally H-2-different B10 (H-2b), B10.D2 (H-2d), or B10.S (H-2s) mice, by contrast, no selection occurred, i.e., the filtered cells were unimpaired in their capacity to kill B10.BR mice. Selection was marked after filtration through H-2-semiallogeneic (B10 X CBA)F1 mice. These data, together with the results of filtering T cells through various H-2 recombinant strains, indicated that selection depended upon the donor and filtration host sharing determinants encoded by both the K- and D-ends of the H-2 complex. Compatibility only in the I region failed to cause demonstrable selection.

Animals↗
PubMed1980

Selection of cytotoxic T-cell precursors specific for minor histocompatibility determinants. I. Negative selection across H-2 barriers induced with disrupted cells but not with glutaraldehyde-treated cells: evidence for antigen processing.

Intravenous injection of CBA mice with H-2-compatible irradiated B10.BR spleen cells led to a sequence of negative and positive selection of the host T-cell response against the multiple foreign minor histocompatibility antigens (HA) on the injected cells. By 1 d posttransfer, thoracic duct lymphocytes (TDL) of the host had lost the capacity to differentiate in vitro into cytotoxic cells specific for the injected minor HA; spleen and lymph node cells, by contrast, gave normal or enriched responses at this time. By 5 d posttransfer, TDL were hyperresponsive to the injected antigens. Selection with disrupted (sonicated) cells gave similar findings. With injection of either irradiated of disrupted spleen cells, the H-2 haplotype of the minor HA-bearing cells had no apparent effect on the magnitude of selection. By contrast, treatment of spleen cells with glutaraldehyde before injection led to H-2 restriction of selection, i.e., negative selection of the CBA response to B10.BR was marked with injection of glutaraldehyde-treated H-2-compatible B10.BR cells but was minimal with H-2-different B10 or B10.D2 cells. These data are taken to imply that, at least in H-2-incompatible situations, the minor HA-bearing cells must be processed by host cells, i.e., to allow the antigens to become associated with self H-2 determinants. Circumstantial evidence from studies on the specificity of selection induced with glutaraldehyde-treated cells from mice of the B10 recombinant strains suggested that I region-restricted T cells may control the induction of H2K, D-restricted cytotoxic precursor cells.

Animals↗
PubMed1978

Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow.

In two situations, transfer of normal unsensitized bone marrow cells into heavily irradiated H-2-identical allogeneic mice caused a high incidence of lethal chronic graft-versus-host disease (GVHD), i.e. mortality occuring between days of 20 and 80 postirradiation. Minor histocompatibility determinants appeared to be the main target for eliciting GVHD. Removing mature T cells from the marrow with anti-Thy 1.2 serum and complement before injection prevented GVHD. On the basis of adding purified T cells to T-cell-depleted marrow cells, it was concluded that contamination of the marrow with as few as 0.3% T cells was sufficient to cause a high incidence of lethal GVHD in certain situations. No GVHD was found with the injection of non-T cells (Thy 1.2-negative cells) or with tolerant T cells. Irradiated recipients of T-cell-depleted marrow cells remained in good health for prolonged periods. These mice showed extensive chimerism with respect to the donor marrow, normal numbers of T and B cells and were immunocompetent. The data provide no support for the view that chronic GVHD developing after bone marrow transplantation in man is the result of an attack by the progeny of the donor stem cells. The results imply that mature T cells contaminating marrow inocula are probably the main cause of GVHD seen in the clinical situation.

Animals↗
PubMedDate not supplied

A phage-linked immunoabsorbant system for the detection of pathologically relevant antigens.

This report describes a novel system for the immunological detection of immobilized antigen. The detection of herpes simplex virus (HSV) antigen was used as an example. Bacteriophage M13, containing the E. coli lac Z gene, was used as the "reporter" molecule in an immunoassay which is otherwise analogous to the enzyme-linked immunoabsorbant assay (ELISA). Briefly, HSV infected cells were incubated with a mouse monoclonal antibody specific for HSV antigen, followed by rabbit anti-mouse serum and mouse anti-M13 serum. Immune complexes were incubated with viable M13 phage. M13 binding was due to the presence of M13 antibodies, whose presence ultimately depended on the binding of monoclonal antibody to HSV. Phage was recovered by elution in pH = 11. Recovered phage was used to infect E. coli. M13 was quantitated by either plaque assay or by an assay for phage-induced beta-galactosidase activity in appropriate E. coli strains. The amount of M13 recovered was proportional to the number of HSV infected cells probed. Therefore, M13 served as a "bio-amplifiable tag" to antibody, as enzymes do in the ELISA. Since M13 is viable, its signal can be amplified by infection of susceptible bacteria, and the promise for an enormously sensitive immunoassay exists. The sensitivity of the assay described here is compared to the ELISA in the detection of HSV infection cells, as an example of the novel assay's potential. Significantly, the novel assay was more sensitive than the ELISA when samples were tested under identical circumstances. This technique is called the phage-linked immunoabsorbant assay (PHALISA), by analogy to the ELISA.

Antigens, Viral↗