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)

Transfusion-associated graft-versus-host disease (TA-GVHD) is one of the most serious adverse effects of blood transfusion. It is generally thought to be caused by the infused lymphocytes. Donor-derived cytotoxic T lymphocytes (CTLs) directed against the recipient's HLAs, which have escaped the recipient's immune system and are proliferating, are considered to attack recipient organs and tissues. Despite the seriousness of the disease, the precise mechanism of its development remains unclear and no definitive treatment has been developed. With the aim of developing an effective treatment, we established and characterized T-cell clones from peripheral blood lymphocytes (PBLs) of a TA-GVHD patient. Three types of clones were established. Type I clones were CD8+ and specifically lyse cells that express HLA B52. Type II clones were CD4+, specifically lysed cells that express HLA DR15, and proliferated in response to stimulation with cells that express DR15. Type III clones were also CD4+, showed no cytotoxic activity toward any HLA-expressing cells, and proliferated in response to stimulation with cells that express DR15. Furthermore, we found that the Fas/Fas-ligand (Fas-L) system is involved in the cytotoxicity of the type I and II clones and that the type III clones produce and secrete a large amount of tumor necrosis factor beta (TNFbeta) after antigen stimulation. Based on our results, these three types of clones can be classified into two categories: those that have the ability to induce GVHD directly by cytolysis and that show no cytotoxic activity and those that have the ability to cause GVHD indirectly through secretion of cytotoxic lymphokines.
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PMID:Characterization of T-cell clones derived from peripheral blood lymphocytes of a patient with transfusion-associated graft-versus-host disease: Fas-mediated killing by CD4+ and CD8+ cytotoxic T-cell clones and tumor necrosis factor beta production by CD4+ T-cell clones. 902 68

The role of T lymphocytes in the control of chronic myeloid leukemia (CML) after bone marrow transplantations has been clearly shown. This effect closely correlates with graft-versus-host disease (GVHD). A specific graft-versus-leukemia (GVL) effect separate from GVHD has been postulated but has been difficult to show. One possible target for specific GVL activity is the bcr-abl fusion protein characteristic of CML. We have investigated the use of normal peptide-pulsed dendritic cells for the generation of cytotoxic, bcr-abl-specific T cells from normal donors. T cells (CD3+, CD8+, TCR alpha beta+, and NK receptor-negative) generated from a normal donor (HLA A24, B52, B59, Cw1) after stimulation with autologous dendritic cells, primed with a 16 mer peptide spanning the b3a2 breakpoint of bcr-abl, lysed CML cells from the peripheral blood of seven patients with CML with the b3a2 breakpoint. CML cells from four patients with only the b2a2 breakpoint were not lysed. Phytohemagglutinin (PHA) blasts derived from peripheral blood of patients with CML were not lysed, suggesting that cytotoxicity was not due to alloreactivity. Blocking experiments with anti-HLA-A,B,C indicated that cytotoxicity was dependent on recognition of major histocompatibility complex (MHC) class I molecules, although cytotoxicity was not MHC-restricted because not all patients shared HLA types with the T-cell donor. Specificity for bcr-abl and absence of alloreactivity was confirmed by the presence of lytic activity against autologous and allogeneic class I HLA-A matched monocytes pulsed with the 16 mer bcr-abl fusion peptide, but not against unpulsed monocytes or monocytes pulsed with other peptides. These results show that bcr-abl-specific T cells with marked cytotoxic activity against CML cells can be generated and amplified from normal donor peripheral blood. Recognition of HLA molecules is essential for cytotoxicity but strict HLA identity is not required.
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PMID:Dendritic cells stimulate the expansion of bcr-abl specific CD8+ T cells with cytotoxic activity against leukemic cells from patients with chronic myeloid leukemia. 944 59