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)

After allogeneic stem cell transplantation, the establishment of the donor's immune system in an antigenically distinct recipient confers a therapeutic graft-versus-malignancy effect, but also causes graft-versus-host disease (GVHD) and protracted immune dysfunction. In the last decade, a molecular-level description of alloimmune interactions and the process of immune recovery leading to tolerance has emerged. Here, new developments in understanding alloresponses, genetic factors that modify them, and strategies to control immune reconstitution are described. In Section I, Dr. John Barrett and colleagues describe the cellular and molecular basis of the alloresponse and the mechanisms underlying the three major outcomes of engraftment, GVHD and the graft-versus-leukemia (GVL) effect. Increasing knowledge of leukemia-restricted antigens suggests ways to separate GVHD and GVL. Recent findings highlight a central role of hematopoietic-derived antigen-presenting cells in the initiation of GVHD and distinct properties of natural killer (NK) cell alloreactivity in engraftment and GVL that are of therapeutic importance. Finally, a detailed map of cellular immune recovery post-transplant is emerging which highlights the importance of post-thymic lymphocytes in determining outcome in the critical first few months following stem cell transplantation. Factors that modify immune reconstitution include immunosuppression, GVHD, the cytokine milieu and poorly-defined homeostatic mechanisms which encourage irregular T cell expansions driven by immunodominant T cell-antigen interactions. In Section II, Prof. Anne Dickinson and colleagues describe genetic polymorphisms outside the human leukocyte antigen (HLA) system that determine the nature of immune reconstitution after allogeneic stem cell transplantation (SCT) and thereby affect transplant outcomethrough GVHD, GVL, and transplant-related mortality. Polymorphisms in cytokine gene promotors and other less characterized genes affect the cytokine milieu of the recipient and the immune reactivity of the donor. Some cytokine gene polymorphisms are significantly associated with transplant outcome. Other non-HLA genes strongly affecting alloresponses code for minor histocompatibility antigens (mHA). Differences between donor and recipient mHA cause GVHD or GVL reactions or graft rejection. Both cytokine gene polymorphisms (CGP) and mHA differences resulting on donor-recipient incompatibilities can be jointly assessed in the skin explant assay as a functional way to select the most suitable donor or the best transplant approach for the recipient. In Section III, Dr. Nelson Chao describes non-pharmaceutical techniques to control immune reconstitution post-transplant. T cells stimulated by host alloantigens can be distinguished from resting T cells by the expression of a variety of activation markers (IL-2 receptor, FAS, CD69, CD71) and by an increased photosensitivity to rhodamine dyes. These differences form the basis for eliminating GVHD-reactive T cells in vitro while conserving GVL and anti-viral immunity. Other attempts to control immune reactions post-transplant include the insertion of suicide genes into the transplanted T cells for effective termination of GVHD reactions, the removal of CD62 ligand expressing cells, and the modulation of T cell reactivity by favoring Th2, Tc2 lymphocyte subset expansion. These technologies could eliminate GVHD while preserving T cell responses to leukemia and reactivating viruses.
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PMID:New developments in allotransplant immunology. 1463 90

The aim of this study was to investigate the ability of CD62L(-)/CD62L(+) T cells responding to antigens so as to explore the role of CD62L in GVHD. The T cells were stimulated by DCs-presenting specific antigen hCD4; the expression of CD62L on surface of T cells was detected by flow cytometry, the CD62(-) T/CD62L(+) T cells were gained by sorting selection method, then were stimulated with a new antigen (freeze-thaw antigen of EL4 cells), and the proliferation activity of CD62L(-) and CD62L(+) T cells was detected by flow cytometry after stimulating with different antigens at twice. The results showed that after stimulating with antigen, the expression level of CD62L(+) on surface of T cells was down-regulated from 60.34% to 36.75%, and the expression of CD62L(-) on surface of T cells increased from 30.04% to 63.15%. Compared with cells counts in area with high CFSE (M1), the average percentages of CD62L(+) T cells under stimulating with specific antigen (hCD4) on days 1 and 6 were (87.88 +/- 1.08)% and (86.88 +/- 1.46)% respectively (p > 0.05), and the average percentages of CD62L(+) T cells after stimulating with specific antigen on days 1 and 6 were (84.52 +/- 2.73)% and (84.21 +/- 2.33)% respectively (p > 0.05), there was no significant difference between two T cell groups on days 1 and 6. After stimulating with non-specific antigen, the average percentages of CD62L(+) T cells in MI area on days 1 and 6 were (76.49 +/- 2.41)% and (22.25 +/- 3.29)% respectively (p < 0.001), the average percentages of CD62l(-) T cells under conditions mentioned above were (77.35 +/- 3.82)% and (74.76 +/- 3.90)% respectively (p < 0.05). The results indicated that the proliferation activity of CD62L(+) T cells appeared, and the proliferation of CD62L(+) T cells did not occur. It is concluded that the CD62L(-) T/CD62l(+) T cells are gained in vitro, no proliferation reaction occurred in these two kinds of cells under stimulation of specific antigen, but the mitotic proliferation occur in CD62L(+) T cells under stimulation of nonspecific antigen, while no this reaction exists in CD62L(-) T cells under this condition. These results provide a new thinking to obtain the CD62L(-) T cells in vitro, to selectively eliminate the CD62L(+) T cells from graft and to decrease occurrence of GVHD in clinical practice.
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PMID:[Proliferative response of CD62L(-)/CD62L(+) T cells in mice to antigen stimulation]. 1923 72