Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Killer cell inhibitory receptors (KIR) are members of the immunoglobulin superfamily (Ig-SF) and transmembrane molecules type I expressed on human natural killer cells and some T lymphocytes. They are ligands for HLA class I antigens. According to the "missing-self" hypothesis, KIR deliver inhibitory signals that prevent target-cell lysis upon binding to the self MHC class I antigens. KIR regulates NK cell function concerned with the control graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (HSCT). The KIR repertoire is substantially influenced by the polymorphic and polygeneic nature of the KIR gene family, and there exist the polymorphism of KIR ligands mainly HLA-C molecule. So it is difficult to achieve the beneficial effect of NK cells on the outcome of partly HLA-mismatched hematopoietic cell transplantation. This review aims to provide background and previous observations on the KIRs which are thought to influence the outcome of HSCT.
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PMID:Killer cell inhibitory receptors involved in graft-versus-host disease and graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation - review. 1515 42

Dendritic cells (DC) play pivotal roles in the induction and regulation of both innate and acquired immunity. DC express several cell-surface immune inhibitory receptors. However, little is known about their potential immunoregulatory functions in the context of T-cell activation. Here we report that murine gp49B, a member of the immunoglobulin superfamily, harboring immunoreceptor tyrosine-based inhibitory motifs, is expressed on DC and downregulates cellular activity to prevent the excessive activation of T cells in vitro and in vivo. Bone marrow-derived DC (BMDC) from newly generated gp49B-deficient (gp49B(-/-)) mice induced enhanced proliferation and IL-2 release of antigen-specific CD4(+) and CD8(+) T cells compared with BMDC from wild-type mice, in a cell-cell contact manner. The enhanced proliferation by gp49B(-/-) BMDC was also observed in allogeneic CD4(+) and CD8(+) T cells. Moreover, the transfer of allogeneic BALB/c splenocytes into C57BL/6 gp49B(-/-) mice induced severe acute graft-versus-host disease with an augmented upregulation of CD86 on CD11c(+) splenic gp49B(-/-) DC, while transfer of C57BL/6 gp49B(-/-) splenocytes into BALB/c mice did not, suggesting the exacerbation of the disease was due, at least in part, to augmented activation of recipient gp49B(-/-) DC. These findings demonstrate a novel regulatory role of gp49B in the function of DC.
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PMID:A novel regulatory role of gp49B on dendritic cells in T-cell priming. 1879 99

The cell surface protein CD83 belongs to the immunoglobulin superfamily and is highly expressed on mature dendritic cells. The soluble form of CD83, sCD83, is a potential immune suppressor. In a previous study, recombinant soluble CD83 was expressed in Escherichia coli, resulting in a lack of functional glycosylation. Although eukaryotic cell systems for producing sCD83 offer the advantages of protein processing, folding, and posttranslational modification, these systems are complicated, expensive, and produce low levels of protein. To obtain more efficient expression of sCD83, we expressed human sCD83 fused with fragment crystallizable region of human IgG1 (hIgG1 Fc) in Pichia pastoris. Under the optimal conditions (time of induction, 48 h; inoculum density (OD600), 80; concentration of methanol, 3.0 %; pH 7.0-8.0; concentration of casamino acid, 5.0 %), the purified human sCD83-hIgG1 Fc (hsCD83-Ig) fusion protein existed as dimers at 25-30 mg/L culture. Treatment with PNGase F showed that purified hsCD83-Ig was modified by N-linked glycosylation. Moreover, the hsCD83-Ig expressed in the P. pastoris system could suppress lymphocyte proliferation in ConA-stimulated and one-way mixed lymphocyte reaction systems. Thus, hsCD83-Ig expressed in P. pastoris is functional and may be used in experimental therapies for graft rejection, graft-versus-host disease, and autoimmune diseases.
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PMID:Production and characterization of human soluble CD83 fused with the fragment crystallizable region of human IgG1 in Pichia pastoris. 2339 67