PubMed · 12044233
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
S J Noga, R Sutherland. 2000. Current methods and new developments in graft evaluation.. https://doi.org/10.1080/146532400539314
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Her-2/neu is a tumor-associated antigen that is expressed on several adenocarcinomas and correlates with poor prognosis. In a previous study (H. J. Bühring et al., Blood, 86: 1916-1923, 1995), it has been demonstrated that Her-2/neu expression can be detected on blast cells from patients with hematological malignancies including acute lymphoblastic leukemia (ALL). Here, we show that Her-2/neu-specific CTLs induced in vitro using peptide-pulsed dendritic cells efficiently lyse primary ALL blasts constitutively expressing both Her-2/neu and human leukocyte antigen A2 in an antigen-specific and MHC-restricted manner. Furthermore, we analyzed the feasibility of this approach in an autologous setting and induced Her-2/neu-specific CTLs using dendritic cells generated from peripheral blood mononuclear cells from an ALL patient that were pulsed with peptides or transfected with in vitro-transcribed Her-2/neu mRNA. Our data demonstrate that Her-2/neu could be used as a potential target for the application of Her-2/neu-directed treatment strategies in ALL including vaccination approaches.
Eph receptor tyrosine kinases and their ligands, the ephrins, have been primarily described in the nervous system for their roles in axon guidance, development, and cell intermingling. Here we address whether Eph receptors may also regulate dendritic cell (DC) trafficking. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that DCs derived from CD34+ progenitors, but not from monocytes, expressed several receptors, in particular EphA2, EphA4, EphA7, EphB1, and EphB3 mRNA. EphB3 was specifically expressed by Langerhans cells, and EphA2 and EphA7 were expressed by both Langerhans- and interstitial-type DCs. EphA and EphB protein expression on DCs generated in vitro was confirmed by staining with ephrin-A3-Fc and ephrin-B3-Fc fusion proteins that bind to different Eph members, in particular EphA2 and EphB3. Immunostaining with anti-EphA2 antibodies demonstrated the expression of EphA2 by immature DCs and by skin Langerhans cells isolated ex vivo. Interestingly, ephrin expression was detected in epidermal keratinocytes and also in DCs. Adhesion of CD34+-derived DCs to fibronectin, but not to poly-l-lysine, was increased in the presence of ephrin-A3-Fc, a ligand of EphA2, through a beta1 integrin activation pathway. As such, EphA2/ephrin-A3 interactions may play a role in the localization and network of Langerhans cells in the epithelium and in the regulation of their trafficking.
Increased risk of graft-versus-host disease (GVHD) has been described in recipients of hematopoietic stem cell transplantations when the donor is a parous woman. Cells from prior pregnancies are now known to persist in women and could contribute to GVHD. We asked whether male DNA (presumed fetal microchimerism) is present in apheresis products of female donors. A total of 50 samples were studied by using real-time quantitative polymerase chain reaction (PCR) for the Y chromosome-specific sequence DYS14. Among 29 growth factor-mobilized peripheral blood mononuclear cell (G-PBMC) products, 34% were positive for male DNA. Quantitative results, expressed as DNA genome equivalent of male cells per million host cells (gEq/mil), ranged from 0 to 35 gEq/mil. Among 21 CD34-enriched cell fractions, 48% were positive with a range of 0 to 357 gEq/mil. In summary, male DNA was frequently detected in G-PBMC and CD34-enriched products from female donors. Whether fetal microchimerism contributes to GVHD merits further investigation.