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)

Graft-versus-host disease (GVHD) is characterized by an impairment of mechanisms that underlie the development of immunologic tolerance. Although the cytokine storm associated with GVHD leads to expression of cell surface markers on both effector and regulatory T cells, regulatory CD4+ T cells that play an instrumental role in the maintenance of tolerance appear to uniquely express the Foxp3 transcriptional repressor. Foxp3 mRNA expression was significantly decreased in peripheral blood mononuclear cells from patients with either allogeneic GVHD or autologous GVHD compared with patients without GVHD. Expression of Foxp3 negatively correlated with the severity of GVHD but positively correlated with recent thymic emigrants. The results suggest that defective thymic function contributes to the impaired reconstitution of immune regulatory mechanisms following transplantation. The decrease in regulatory mechanisms after transplantation appears to provide an environment permissive to the development of GVHD.
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PMID:Association of Foxp3 regulatory gene expression with graft-versus-host disease. 1517 73

Peripheral suppression of autoreactive T cells by specialized T-cell populations is one of several mechanisms ensuring self-tolerance within the adaptive immune system. Thymus-derived CD4+CD25+ T cells expressing the transcriptional repressor FOXP3 mediate such immunoregulatory functions and are pivotal for the prevention of autoimmunity. As peripheral tolerance induction is a prerequisite for successful treatment outcome after allogeneic hematopoietic stem cell transplantation (HSCT), the role of CD4+CD25+ T cells in transplantation models and clinical trials is now under investigation in many laboratories. Here we summarize recent results regarding protection from graft-versus-host disease (GVHD) by adoptively transferred CD4+CD25+ T cells in mice and discuss early findings from clinical studies in HSCT.
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PMID:CD4+CD25+ regulatory T cells and graft-versus-host disease. 1641 90

Development of naturally occurring CD4+CD25+ T regulatory cells (Treg) in the thymus requires the transcription factor Foxp3. Major histocompatibility complex (MHC) class II, self-ligands expressed by epithelial cells, and thymic stromal lymphopoietin also appear to play important roles. In addition, several molecular regulators of T-cell receptor (TCR) signaling (both positive and negative) have been implicated in the control of Treg development. Foxp3 is a transcriptional repressor of IL-2 and other cytokines and appears to maintain the anergic and suppressor function of these cells. Multiple cell types (T cells, B cells, dendritic cells [DC], and natural killer [NK] cells) are targeted by Treg using diverse suppressor mechanisms, whereas factors that regulate Treg proliferation and function, including Toll-like receptor (TLR) ligands, have also been identified. Because Treg play an important role in the control of autoimmunity, therapeutic strategies are being pursued to enhance their numbers and function in specific autoimmune diseases. In transplantation, where Treg also offer potential for therapy of rejection and graft-versus-host disease (GVHD), indirect allorecognition may be the dominant pathway for immune regulation by these cells. In tumor immunology, Treg have emerged as major suppressors of T-cell-mediated antitumor responses and represent a significant obstacle to effective anticancer vaccines. Strategies aimed at depletion/functional inhibition of these cells by molecular targeting must maintain a critical balance between tumor immunity and self-tolerance.
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PMID:Naturally occurring regulatory T cells: recent insights in health and disease. 1743 97