Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of methods of avoiding graft-versus-host disease (GVHD) while retaining the alloengraftment-promoting and anti-leukemic effects of allogeneic T cells is a major goal of research in bone marrow transplantation (BMT). We have recently obtained evidence suggesting that natural suppressor (NS) cells derived from T cell-depleted (TCD) syngeneic marrow can protect against GVHD while permitting alloengraftment. We have now attempted to enrich and then propagate NS cells in vitro, with the goal of obtaining an enhanced anti-GVHD effect by adoptive transfer in vivo. Two long-term cell lines were generated culturing BMC depleted of Mac1-positive cells and of Mac1-positive plus Thy1-positive cells in high concentrations of IL-2. Both cell lines showed anti-GVHD effects when administered along with a GVHD-producing inoculum, while permitting complete allogeneic reconstitution. A clone derived from Mac1-depleted BMC protected completely against a more chronic pattern of GVHD. These cell lines demonstrated suppressive activity in vitro, cytolytic activity against a broad range of natural killer (NK)-sensitive and NK-resistant targets, and a novel cell surface phenotype, with characteristics of both alpha beta-TcR-bearing T cells and of NK cells. In some respects, these cells resemble LAK cells and differ from fresh NS cells, and from the cloned NS cells derived from spleens of total lymphoid irradiation (TLI)-treated mice and neonatal mice. To our knowledge, this is the first detailed phenotypic analysis of cell lines with in vivo anti-GVHD activity. If applicability can be demonstrated in large animal models, the ability to use bone marrow as a source of such protective cell lines might also have potential utility in clinical BMT.
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PMID:In vitro and in vivo analysis of bone marrow-derived CD3+, CD4-, CD8-, NK1.1+ cell lines. 214 39

The survival of skin grafts from B6.C-H-2bm1 (bm1; Kbm1,IAb,IE-,Db) mice was prolonged when C57BL/6 CrSlc (B6; H-2b) mice were inoculated intravenously with 9 x 10(7) spleen cells (SC) plus 3 x 10(7) bone marrow cells from bm1 mice 14 days prior to skin grafting. When B6 mice were inoculated i.v. with bm1 cells and treated intraperitoneally with 200 mg/kg cyclophosphamide (CP) 2 days later, the survival of bm1 skin grafts was not prolonged at all, suggesting antagonism between the veto cell-mediated enhancement by donor cells and CP-induced enhancement. In order to deplete the veto cells from the tolerogen, SC plus BMC were treated with anti-Thy1.2 mAb+C' or CP. The survival of the bm1 skin grafts was not prolonged at all in B6 mice inoculated with Thy1.2-treated bm1 or bm1 cells from CP-treated donors. When B6 mice were inoculated with Thy1.2-treated or CP-treated bm1 cells and followed by CP treatment, however, the survival of bm1 skin grafts was prolonged moderately. These results strongly suggested that the unresponsiveness induced with donor-derived veto cells prevents the tolerance induction to class I alloantigens (H-2Kbm1) by our protocol of CP-induced tolerance. Furthermore, in B6 mice injected with anti-Thy1.2 mAb on day -1 and bm1 cells on day 0, the survival of bm1 skin grafts was not prolonged at all. However, skin graft tolerance to bm1 antigens was induced when B6 mice were injected with anti-Thy1.2 mAb on day -1 and bm1 cells on day 0 followed by CP on day 2. These results may also be explained by the depletion of donor-derived veto cells in the recipient mice.
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PMID:Prevention of induction of unresponsiveness to class I antigens by veto activity of donor marrow in cylophosphamide-treated mice. 827 22