These results suggest that trimeric H-2Kd complexes (i
These results suggest that trimeric H-2Kd complexes (i.e. cells, all three lines expressed H-2K cDNA sequences identical to those of d-haplotype BALB/c mice, as well as constitutive and cytokine-inducible H-2Kd determinants. In contrast, apart from H-2Ld[LOW] display in 3(8)21 cells, H-2Dd, H-2Ld and I-Ad determinants were undetectable. All three lines expressed constitutive and cytokine-inducible CD34; however, except VCE-004.8 for inducible CD117[LOW] expression in 3(8)21 cells, no expression of CD45, CD117, CD62L, CD80, CD86, CD901 or CD95L/CD178 was observed. Constitutive and cytokine-inducible CD95[LOW] expression was detected in STO and 3(8)21 cells, but not in 3(8)21-EGFP cells. MHC (class I+[LOW]/class II?) and CD (CD34+/CD80?/CD86?/CD95L?) expression patterns in STO and STO cell-derived progenitor cells resemble patterns reported for human embryonic stem cell lines. Whether these patterns reflect associations with mechanisms that are regulatory of immune privilege or functional tissue-specific plasticity is unknown. survival of human bone marrow-derived mesenchymal stem cells (MSCs) grafted xenogeneically into sheep,4 several tissues including the brain,5 eye,6 uterine cervix,7 pregnant uterus,8 testis9 and ovary10 are well-known sites of immune privilege. However, foreign grafts usually do not encounter immune-privileged sites. Thus, immunosuppressive treatments are essential to sustain graft survival, although they are frequently toxic and VCE-004.8 often lead to significant patient morbidity and death.11,12 To circumvent clinical management problems and to provide competent xenogeneic or allogeneic grafts, various systems of pluripotential stem or progenitor cells that express syngeneic host histocompatibility antigens or display intrinsic immune privilege are under investigation as models for xenogeneic or allogeneic transplantation in non-immunosuppressed hosts.13 For example, human embryonic stem (hES) cell lines, generated either by somatic cell nuclear transfer (SCNT) in enucleated human oocytes or by fusion and reprogramming of adult somatic cells, have been proposed as sources of patient- and organ-specific donor cells.14C17 Although the engraftment and functional properties of cloned and reprogrammed ES and SCNT cells have yet to be demonstrated, transplantation studies with conventional hES and non-human stem, MSC or progenitor cell systems in non-immunosuppressed hosts have been described.18C24 Properties of this group of immune-privileged systems, summarized in Table 1, suggest the following trends: firstly, the incidence of class I[LOW] expression is higher than that of non-expression; secondly, none of the cells expresses MHC/human leucocyte antigen (HLA) class II determinants; thirdly, graft survival times vary markedly, from 2 to 90 days; and, lastly, common patterns and mechanisms of intrinsic immune privilege have not yet emerged.18C25 Furthermore, the biological status of the xenogeneic and allogeneic grafts in several reported situations is questionable:18C22 for example, potential artifacts caused by unwanted donor cell fusion with recipient cells,26C29 by genomically integrated vectors and reporter genes, or by transfection of recipient cells with naked DNA released from dying donor cells have yet to be eliminated; in one investigation, primary data were lacking.22 Table 1 Experimental models of immune-privileged stem and progenitor cells or cell lines transplanted in non-immunosuppressed histoincompatible hosts VCE-004.8 MHC/HLA status of donor cellsIFN- inducibilitytreatment with exogenous IFN-, a potent cytokine inducer of H-2 gene expression,34 raised the possibility of intracellular H-2Kq expression defects Rabbit polyclonal to LDLRAD3 at various levels. To ascertain the basis of undetectable MHC expression and its potential role in mechanisms of intrinsic immune privilege displayed by STO and SCD cells, and to determine if these cells express either CD antigens, such as CD34 (haematopoeitic stem cell antigen35), CD45 [leucocyte common antigen (LCA)36] and CD117 (stem cell factor c-receptor37), which are associated with normal stem cells, or molecules associated with MHC-independent forms of tolerance such as the CD95 (Fas)-CD95L/CD178 (Fas-ligand) system,38,39 STO and SCD progenitor cell lines were investigated further for prominent sets of MHC-related molecules and CD antigens by.