Linked Life Data

1831826

Source:http://linkedlifedata.com/resource/pubmed/id/1831826

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1991-9-27
pubmed:abstractText
The role of host anti-donor cells in rejection of fully allogeneic donor T cell-depleted marrow was investigated by using mAb or immunotoxins directed against T cell or NK cell determinants. Immunotoxins consisting of mAb conjugated to a low oligosaccharide-containing fraction of purified ricin toxin A chain (RTA) facilitated in vivo-depletion of target cell populations. BALB/c and DBA/1 donors were selected based upon their expression (BALB/c) or lack of (DBA/1) hemopoietic histocompatibility (Hh1) Ag, which may serve as targets for donor rejection in C57BL/6 hosts. When studies directed toward eliminating CD3+ cells were performed in both systems, injections of intact anti-CD3 mAb or anti-CD3-RTA reproducibly produced the highest engraftment values. The fact that engraftment values obtained with anti-CD3 or anti-CD3-RTA therapy in allogeneic systems were substantially higher than in syngeneic controls suggested that engraftment stimulatory proteins were released upon TCR engagement. Elevated levels of cytokines and a high mortality rate in allogeneic recipients confirmed that this was the case. Nonstimulatory preparations of anti-CD3F(ab')2 fragments and anti-CD3F(ab')2-RTA promoted engraftment of both types of allogeneic marrow, as measured by short term 125I-IUdR assays, suggesting that stimulation was not a prerequisite for engraftment. Recipients of anti-CD3F(ab')2 or anti-CD3F(ab')2-RTA showed a marked reduction of host CD3+ cells as measured by immunofluorescence and flow cytometry. In long term chimerism studies, recipients of Hh1-disparate marrow and anti-CD3F(ab')2 had a dramatic increase in donor cell engraftment as compared to controls, indicating that positive effects on engraftment were long lived. Studies further showed that BALB/c donor cells exhibiting an Hh1 disparity were rejected by host cells expressing NK1.1 or Ly-1 (NK cells and T cells). In contrast, DBA/1 donor cells that were not Hh1-disparate were rejected by cells expressing Ly-1, but not NK1.1 (T cells only). These studies provide definitive data that CD3+ cells participate in the rejection of either Hh1+ or Hh1null T cell-depleted allografts and offer new strategies for alloengraftment using regimens containing nonmitogenic anti-CD3.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
147
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1492-503
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:1831826-Animals, pubmed-meshheading:1831826-Antibodies, Monoclonal, pubmed-meshheading:1831826-Antigens, CD3, pubmed-meshheading:1831826-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:1831826-Antigens, Ly, pubmed-meshheading:1831826-Bone Marrow Transplantation, pubmed-meshheading:1831826-Cytokines, pubmed-meshheading:1831826-Immunoglobulin Fab Fragments, pubmed-meshheading:1831826-Immunotoxins, pubmed-meshheading:1831826-Killer Cells, Natural, pubmed-meshheading:1831826-Lymphocyte Activation, pubmed-meshheading:1831826-Lymphocyte Depletion, pubmed-meshheading:1831826-Mice, pubmed-meshheading:1831826-Mice, Inbred Strains, pubmed-meshheading:1831826-Receptors, Antigen, T-Cell, pubmed-meshheading:1831826-Skin Transplantation, pubmed-meshheading:1831826-T-Lymphocytes
pubmed:year
1991
pubmed:articleTitle
In vivo administration of anti-CD3 monoclonal antibodies or immunotoxins in murine recipients of allogeneic T cell-depleted marrow for the promotion of engraftment.
pubmed:affiliation
Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis 55455.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't