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Biomedical subjects

J Michaelson

Publications and source records attributed to J Michaelson.

16 recordsLinked to original sources
PubMed1991

Lymphocytes with a CD4+ CD8- CD3- phenotype are effectors of experimental cutaneous graft-versus-host disease.

Graft-versus-host disease (GVHD) is known to cause profound dysregulation of the immune system, although its effector mechanisms are poorly understood. We now describe an effector lymphocyte of unusual phenotype in the skin of mice with GVHD. This cell is of donor origin and expresses several T-cell surface proteins including Thy-1, CD2, and CD4 but does not express CD8, CD3, NK1.1, or macrophage antigens. Mononuclear cells of this phenotype are the predominant lymphocyte in the epidermis of mice with GVHD 3 weeks after transplant but are not detected in transplanted mice without GVHD. Isolation and transfer of these lymphocytes into secondary recipients causes epidermal damage characteristic of GVHD. These data demonstrate that CD4+ CD8- CD3- lymphocytes are an important effector population that can be amplified outside the thymus and that can mediate target organ damage of GVHD.

Animals↗
PubMed1990

Evidence for an intrinsic B cell defect in lpr/lpr mice apparent in neonatal chimeras.

Stem cells from a lpr/lpr mouse do not cause the lpr syndrome characteristic of unmanipulated MRL/lpr mice when injected into nonautoimmune neonatal mice. Instead, these neonatal chimeras gradually become markedly lymphopenic. As adults, only limited donor cell engraftment (approximately 5%) was evident as assessed by cell surface staining of H-2D or Thy-1 allelic markers. However, the relatively low number of lpr/lpr-derived B cells produced greater than 90% of the circulating IgG2a antibody and all detectable IgG2a anti-ssDNA autoantibody, indicating that lpr/lpr B cells express an intrinsic genetic defect resulting in hyper-IgG and autoantibody secretion.

Animals↗
PubMed1990

Evidence that anti-asialo GM1 in vivo improves engraftment of T cell-depleted bone marrow in hybrid recipients.

Engraftment of T cell-depleted bone marrow was studied in a P----F1 murine bone marrow transplant model which features long-term stability of mixed chimerism of donor (B6) and host (B6AF1) cells after BMT. We report that a polyclonal antibody to asialo GM1 (anti-ASGM1) given in vivo after transplant was able to increase long-term donor bone marrow engraftment. In vivo anti-ASGM1 eliminated NK activity but did not affect the generation of cytotoxic T cells nor did it stimulate hematopoiesis in vitro. Anti-Thy 1.2, a pan-T cell monoclonal antibody, had no effect on donor engraftment. We conclude that ASGM1+ cells with NK activity inhibit the long-term engraftment of bone marrow stem cells in this model and that antibodies to NK cells can be used in vivo as an effective component of the transplant conditioning regimen.

Animals↗
PubMed1988

Engraftment following T cell-depleted bone marrow transplantation. III. Differential effects of increased total-body irradiation on semiallogeneic and allogeneic recipients.

Three different doses of total-body irradiation (TBI) (1100, 1300, 1500 cGy) have been analyzed as conditioning regimens for semiallogeneic B6AF1 (H-2b X H-2a) and allogeneic A/J (H-2a) recipients of T cell-depleted C57BL6 (H-2b) bone marrow transplants. Recipient survival and engraftment of both donor erythrocytes and lymphocytes were examined in each group. The large majority of allogeneic mice prepared with 1100 cGy rejected their grafts, which resulted in poor survival (less than 30%); improved survival (up to 80%) and complete donor engraftment were noted as the TBI dose was increased. By contrast, survival in semiallogeneic B6AF1 recipients was independent of TBI dose and was greater than 80% in all groups. Outright failure of marrow grafts (less than 10% donor hematopoiesis) did not occur in these recipients, but mixed chimerism (simultaneous occurrence of both donor and host cells) was frequently observed at lower TBI doses. Complete (greater than 90%) donor engraftment was noted for erythrocytes but not for lymphocytes. Possible mechanisms accounting for these differences between semiallogeneic and allogeneic recipients of marrow transplants are discussed.

Animals↗
PubMed1987

Selective elimination of non-lpr lymphoid cells in mice undergoing lpr-mediated graft-vs-host disease.

The transfer of lpr BM stem cells into lethally irradiated non-lpr recipients (including the congenic MRL/+ differing only at the lpr locus) causes GVHD characterized by a wasting syndrome. In this study we investigated the interaction between the autoimmune (lpr) and normal (A-Thy) B, T, and RBC cell lineages in two types of radiation chimeras: MRL/lpr plus A-Thy----(MRL/lpr X A-Thy)F1 and MRL/+ plus A-Thy----(MRL/lpr X A-Thy)F1. Analysis of B cell repopulation by competitive RIA of serum Igh-1 allotype showed that both the MRL and the A-Thy donor cells initially engrafted. However, by 2 to 4 mo post-transplantation the normal A-Thy allotype was barely detectable (reduced greater than 2 orders of magnitude), whereas the autoimmune MRL/lpr allotype persisted at normal levels. Similarly, investigation of the donor origin of peripheral blood T cells by two-color flow cytometry showed that by 8 mo post-transplantation normal A-Thy T cells had been eliminated and only MRL/lpr T cells were present in the circulation. In contrast, erythrocytes from both the MRL/lpr and A-Thy donor strains successfully engrafted the F1 recipients and persisted until the termination of the study. Control chimeras transplanted with a mixture of MRL/+ plus A-Thy BM were stably engrafted with both donor strains in both the erythroid and lymphoid populations. Additional experiments in which either B6/lpr or MRL/lpr (and B6/+ or MRL/+ control) BM cells were transferred into (MRL/lpr X B6/+)F1 and (MRL/lpr X B6/lpr)F1 recipients demonstrated that the development of GVHD was not simply due to increased alloreactivity by the lpr donor cells. In these chimeras only the recipients heterozygous (but not homozygous) for the lpr gene developed lpr-GVHD, although both types of recipients had identical genotypes except at the lpr locus.

Animals↗
PubMed1987

The lpr gene is associated with resistance to engraftment by lymphoid but not erythroid stem cells from normal mice.

This study demonstrates cell lineage-specific resistance to engraftment involving lymphocytes but not erythrocytes by the spontaneously autoimmune MRL/lpr mouse strain. In these experiments, MRL/lpr mice were lethally irradiated (1000 R) and reconstituted with normal A-Thy bone marrow stem cells. Periodic analysis from 6 wk to 6 mo posttransplantation demonstrated that the T and B cells of these chimeras were derived from the MRL/lpr host. However, in the same A-Thy----MRL/lpr chimeras, erythrocyte repopulation was completely of A-Thy donor origin. In contrast, control MRL/+ (congenic mice that differ from MRL/lpr at the lpr locus and do not develop accelerated autoimmune disease) recipients were successfully repopulated in both the lymphoid and erythroid compartments by the A-Thy donor cells.

Animals↗
PubMed1987

Engraftment following T-cell-depleted bone marrow transplantation. II. Stability of mixed chimerism in semiallogeneic recipients after total-body irradiation.

Chronic, stable mixed chimerism of both lymphocytes and erythrocytes was observed in semiallogeneic murine recipients of T-cell-depleted bone marrow transplants that had been conditioned with supralethal total-body irradiation (1100 cGy). Mixed chimerism was extensive, with a wide range of donor engraftment persisting for at least one year after transplant. In both erythrocyte and lymphocyte lineages, decreasing donor engraftment correlated with decreasing marrow dose; however, complete red cell engraftment was more easily achieved than complete lymphocyte engraftment. There were no late graft failures, even among animals exhibiting a substantial host component of hematopoiesis. The extent of mixed hematopoietic chimerism therefore appears to be much greater than had been expected in recipients of T-cell-depleted bone marrow transplants.

Animals↗
PubMed1986

Biochemical genetics of TL antigens.

TL antigens are class I glycoproteins which are expressed on thymocytes and which are coded by the Tla region of the major histocompatibility complex of the mouse. Biochemical analysis of TL molecules from different strains of mice revealed structural variation determined by the Tla region which is detectable by peptide mapping, isoelectric focusing, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, two-dimensional gels, and by differential reactivity of allelic forms of TL molecules with a panel of anti-TL reagents. The quantity of TL expressed on thymocytes is also influenced by the Tla region; three quantitative phenotypes were identified: high (Tlaa, Tlad, Tlae), intermediate (Tlac, Tlaf), and low (Tlab). (Relative amounts: 1000: 100: 1.) Some thymic leukemias arising in (Tlab, Tlac) mice with genetically determined reduced levels of thymic TL were found to express TL molecules which were structurally indistinguishable from TL isolated from thymocytes but were present in larger amounts. This suggests that TL structural genes are intrinsically capable of full expression in all mice but that the Tla region of mice expressing an intermediate or low quantity of TL is marked by some feature which causes the thymocyte to express less than the full amount of TL possible.

Age Factors↗
PubMed1986

Unusual association of beta 2-microglobulin with certain class I heavy chains of the murine major histocompatibility complex.

Class I products of the major histocompatibility complex (MHC) comprise a heavy chain of about 45 kDa noncovalently linked to a 12-kDa beta 2-microglobulin (beta 2m) light chain encoded on a different chromosome. We find that class I products of some mouse strains include an additional 62-kDa molecule which on the following evidence consists of a heavy chain linked covalently with beta 2m. Production of the 62-kDa protein invariably accorded with the occurrence of cysteine at position 121 of the heavy chain (Kb,Kbm1,Kbm3,Dd, and Ld). Substitution of arginine at position 121 invariably accorded with absence of the 62-kDa protein (Kbm6,Kbm7,Kbm9,Kd, and Db). On the basis of observed production versus nonproduction of the 62-kDa molecule, predictions are made regarding residue 121 in class I products for which this is not yet known; namely, Kk, Ks, and Dk, which produce the 62-kDa molecule, as compared with Kj, Qa-2, and TL, which do not. Reported differences in immunologic reactivity between Kb mutant strains with Arg-121 in place of Cys-121 imply that the occurrence of 62-kDa class I products in mice of Cys-121 genotype has functional consequences.

Alleles↗
PubMed1979

A cell surface antigen, TER, expressed by embryos and germ cells.

An antiserum prepared in rabbits against the C3HeB/FeJ mouse ovarian teratocarcinoma E6496 was absorbed in vivo in C3HeB/FeJ mice. This absored antiserum identified an antigen, denoted TER, that is present on sperm, ova, embryonic germ cells, and cells of the early mouse embryo. TER was absent from all adult somatic cells tested, but found on several murine tumors.

Absorption↗
PubMed1977

Molecular similarities between the Qa-2 alloantigen and other gene products of the 17th chromosome of the mouse.

The alloantigen Qa-2, whose gene is located on the 17th chromosome between H-2D and Tla, is identified as a molecule of 43,000 daltons which is associated with beta 2-microglobulin. Qa-2 comprises approximately 0.15% of the iodinateable cell surface protein of lymph node cells. Sequential precipitations demonstrated that Qa-2 is distinct from H-2D and H-2K molecules.

Animals↗
PubMed1974

Evaluation of bis-benzimidazoles in the treatment of murine lymphocytic choriomeningitis virus infections.

Seventy percent of the mice receiving (S,S)-1,2-bis(5-methoxy-2-benzimidazolyl)-1,2-ethandiol (A36683) in their drinking water lived at least four times longer than control mice when infected with 10 or 100 mean lethal doses of lymphocytic choriomeningitis virus strain UBC. In the next 4 months, most of the survivors died with lymphocytic choriomeningitis-like symptoms. Drug treatment during the first 7 days after infection was found to have no significant effect on virus titers in various organs. The sparing effect of the drug is discussed in terms of immunosuppression.

Animals↗