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)

Human dendritic cells (DC) generated from CD34+ hematopoietic progenitors cultured in the presence of granulocyte macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha are related to Langerhans cells (DLC) and have been shown to induce a strong proliferation of allogeneic CD4+ T cells. The present study shows that recombinant human IL-10 (h-IL-10) inhibits the primary and secondary proliferative responses of both CD4+ and CD8+ T cells induced by allogeneic CD1a+ DLC. The alloreaction induced by DLC generated after 5-18 days of culture of CD34+ HPC was equally inhibited by h-IL-10, thus indicating that DLC were sensitive to h-IL-10 at all stages of differentiation. This is further indicated by the h-IL-10-induced inhibition of the T cell alloreaction mediated by interdigitating DC freshly isolated from tonsils. h-IL-10 specifically acted on DLC as it did not affect the proliferation induced by Epstein-Barr virus lymphoblastoid cell lines (EBV-LCL) nor that induced by immobilized anti-CD3. The inhibitory effect of h-IL-10 was not due to the production of suppressive factors by the DLC, as the addition of DLC and IL-10 did not inhibit EBV-LCL-induced T cell proliferation. Rather, the inhibition of cytokine production (IL-2, GM-CSF, TNF, IFN-gamma) observed after 24 h of co-culture may explain the inhibition of T cell DNA synthesis detected 3 days later. The h-IL-10-induced inhibition of human DC mediated alloreaction advocates considering the use of h-IL-10 in the prevention of transplant rejection and graft versus host disease, phenomena initiated by DC.
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PMID:Interleukin 10 inhibits T cell alloreaction induced by human dendritic cells. 752 90

The phenomenon of microchimerism and its relationship to long-term graft tolerance is an area of active study. The ability to establish a tolerant state has been enhanced with current immunosuppressive drugs and emerging therapies such as donor HPC infusions. An undesirable outcome of host-donor WBC interaction is GVHD. GVHD is a rare complication reported most frequently in liver transplantation. Two cases of GVHD reported in recipients of organs from donors homozygous for a shared HLA haplotype would support a policy of avoiding the use of these donors. TA-GVHD is very rare in solid organ transplant recipients, with only four published cases; only two had convincing supportive evidence and one of these had an underlying hematologic abnormality. These few cases do not support a policy of routine irradiation of cellular blood components for all solid organ transplant recipients. The use of donor HPC infusions to enhance chimerism and graft tolerance has increased the number of GVHD cases observed (usually mild) and decreased the severity and number of rejection episodes. The long-term effects of donor HPC infusions on graft survival is under investigation.
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PMID:Microchimerism, GVHD, and tolerance in solid organ transplantation. 1127 1