Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-15 (IL-15) is a gamma-common cytokine that plays an important role in the development, survival, and proliferation of natural killer (NK), NK T, and CD8+ T-cells. We administered IL-15 to recipients of an allogeneic bone marrow transplantation (allo BMT) to determine its effects on immune reconstitution. Posttransplantation IL-15 administration significantly increased donor-derived CD8+ T (mostly CD122(+)CD44(+)CD8+ T-cells), NK, and NK T-cells at day +28 in young and old recipients of allo BMT. This was associated with enhanced T-cell and NK-cell function. IL-15 stimulated homeostatic proliferation of donor CD8+ T-cells in recipients of carboxyfluorescein diacetate succinimidyl ester-labeled donor T-cell infusions. Posttransplantation IL-15 administration also resulted in a decrease in apoptotic CD8+ T-cells, an increase in Bcl-2-expressing CD8+ T-cells, and an increase in the fraction of Ki67+ proliferative NK and CD8+ T-cells in recipients of allo BMT. IL-15 did not exacerbate graft-versus-host disease (GVHD) in recipients of T-cell-depleted BMT but could aggravate GVHD in some cases in recipients of a T-cell-repleted BMT. Finally, we found that IL-15 administration could enhance graft-versus-leukemia activity. In conclusion, IL-15 can be administered safely to recipients of a T-cell-depleted allo BMT to enhance CD8+ T, NK, and NK T-cell reconstitution.
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PMID:Interleukin-15 enhances immune reconstitution after allogeneic bone marrow transplantation. 1528 Feb 5

Graft-vs-host disease (GVHD) is caused by a donor T cell anti-host reaction that evolves over several weeks to months, suggesting a requirement for persistent alloreactive T cells. Using the C3H.SW anti-C57BL/6 (B6) mouse model of human GVHD directed against minor histocompatibility Ags, we found that donor CD8(+) T cells secreting high levels of IFN-gamma in GVHD B6 mice receiving C3H.SW naive CD8(+) T cells peaked by day 14, declined by day 28 after transplantation, and persisted thereafter, corresponding to the kinetics of a memory T cell response. Donor CD8(+) T cells recovered on day 42 after allogeneic bone marrow transplantation expressed the phenotype of CD44(high)CD122(high)CD25(low), were able to homeostatically survive in response to IL-2, IL-7, and IL-15 and rapidly proliferated upon restimulation with host dendritic cells. Both allogeneic effector memory (CD44(high)CD62L(low)) and central memory (CD44(high)CD62L(high)) CD8(+) T cells were identified in B6 mice with ongoing GVHD, with effector memory CD8(+) T cells as the dominant (>80%) population. Administration of these allogeneic memory CD8(+) T cells into secondary B6 recipients caused virulent GVHD. A similar allogeneic memory CD4(+) T cell population with the ability to mediate persistent GVHD was also identified in BALB/b mice receiving minor histocompatibility Ag-mismatched B6 T cell-replete bone marrow transplantation. These results indicate that allogeneic memory T cells are generated in vivo during GVH reactions and are able to cause GVHD, resulting in persistent host tissue injury. Thus, in vivo blockade of both alloreactive effector and memory T cell-mediated host tissue injury may prove to be valuable for GVHD prevention and treatment.
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PMID:Alloreactive memory T cells are responsible for the persistence of graft-versus-host disease. 1572 19

Small bowel transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients where total parenteral nutrition (TPN) therapy for intestinal failure is unsuccessful. Early referral for screening for small bowel transplantation should be considered in patients with permanent intestinal failure who have occlusion of more than 2 major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies, the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation and is further improving. Rejection, bacterial, fungal and viral (Cytomegalovirus, Epstein-Barr-virus) infections, post-transplant lymphoproliferative disease and graft versus host disease are the most common complications after intestinal transplantation. Although most of the long-term survivors are TPN-independent and have a good quality of life, the risk of the procedure and long-term adverse effects ofimmunosuppressive medication limits small bowel, or liver/small bowel transplantation only to patients with severe complications of TPN therapy.
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PMID:[Small bowel transplantation as a treatment option for intestinal failure in children and adults]. 1575 17

Steroid-resistant acute GVHD (aGVHD) following allogeneic hematopoietic stem cell transplantation (alloHSCT) continues to be associated with a high mortality. We report the results of a phase II study of treatment of steroid-resistant aGVHD with the IL-2 receptor antibody daclizumab combined with the TNF-receptor fusion protein etanercept. Treatment consisted of daclizumab 1 mg/kg given i.v. on days 1, 4, 8, 15, 22 and etanercept 16 mg/m(2) s.c. on days 1, 5, 9, 13, 17. A total of 21 patients (age 15-61 years) with steroid-resistant aGVHD after alloHSCT were included in the study. Donor types were HLA-matched related (n=6), HLA-matched unrelated (n=14), and HLA-mismatched unrelated (n=1). Eight patients achieved complete, and six showed partial remission of aGVHD. Seven patients did not respond. Four of 21 patients are currently alive with a median follow-up of 586 (185-1155) days. Three patients died due to relapsed malignancy. Treatment-related mortality was due to infectious complications (n=11) or organ failure due to aGVHD (n=3). In total, 12 patients developed subsequent chronic GVHD. In conclusion, the data demonstrate an acceptable response rate of the combination of daclizumab and etanercept in the treatment of steroid-resistant aGVHD. Nevertheless, long-term mortality due to infectious complications and chronic GVHD remains high.
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PMID:Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept. 1580 35

Graft-versus-host disease (GvHD) complicates many allogeneic stem cell transplants (alloSCT), and several factors are known to be associated with the development of GvHD besides human leucocyte antigen (HLA) incompatibility. We investigated whether changes in serum levels of soluble IL-2 receptor (sIL-2Ralpha), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), vascular endothelial growth factor (VEGF) and soluble Fas (sFas) correlated with the development of GvHD in patients undergoing SCT, and might thus be potentially of use to anticipate the development of GvHD, allowing early modification of immunosuppressive therapy.sIL2Ralpha and sFas levels were significantly raised in allograft, autograft (allo and auto) and non-graft groups compared to the normal controls (HC), but there was no statistical difference between the three patient groups. TNF-alpha was raised in the auto and allo groups and the non-graft patients compared to the HC group (median 4.37 pg/ml), but only reached significance in the allo group (median 6.02 pg/ml; p = 0.008) when this was compared with the non-graft patients. There was no significant difference in TGF-ss levels between any of the groups. The median serum VEGF levels were decreased in allo and auto patients compared to HC, (31 and 62 pg/ml versus 90 pg/ml, respectively), with a significant difference in the auto group (p = 0.007). VEGF levels were significantly lower in the auto versus the allo group (p = 0.008) and also in the auto versus the non-graft group (median 104 pg/ml; p = 0.011). When the allo group was divided into patients who developed GvHD and those who did not, serum VEGF levels were significantly higher in those with GvHD (p = 0.028).
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PMID:Cytokine profiles in stem cell transplantation: possible use as a predictor of graft-versus-host disease. 1601 56

Acute graft-versus-host disease (aGVHD) occurs in up to 80% of patients who undergo allogeneic stem cell transplantation (SCT) and contributes significantly to transplant-related mortality (TRM). We conducted a prospective phase II trial to assess the efficacy and feasibility of treating steroid-refractory aGVHD with basiliximab, a chimaeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor. Basiliximab was administered intravenously at a dose of 20 mg on days 1 and 4. Twenty-three patients were enrolled between October 1999 and July 2004. We found a primary overall response rate of 82.5% with four patients (17.5%) showing a complete response and 15 patients (65%) a partial response. Six patients were again treated successfully with an IL-2 receptor antagonist because of recurrence of aGVHD. The rates of infections, chronic GVHD, malignancy recurrence and 1-year TRM following immunosuppression with basiliximab were comparable with those found with other treatment modalities for aGVHD. We conclude that basiliximab is efficient and feasible for steroid-refractory aGVHD and merits further evaluation.
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PMID:Efficacy of the interleukin-2 receptor antagonist basiliximab in steroid-refractory acute graft-versus-host disease. 1609 72

Daclizumab, a humanized IL-2 receptor antagonist, has been found to be safe and effective in adults with refractory graft-versus-host disease (GVHD); however, data describing its efficacy for refractory GVHD in children are limited. We report a series of 14 children who were treated with daclizumab for severe acute and/or chronic corticosteroid refractory GVHD. Patients were treated with 2 mg/kg weekly for 8 weeks followed by 1 mg/kg weekly for 4 weeks. Nine of 14 patients responded to daclizumab as measured by improvement of GVHD symptoms, and the ability to substantially wean corticosteroid dose. Five of 11 patients with acute GVHD had complete symptom resolution, and 2/11 had a partial response. Two of four patients with chronic GVHD had complete symptom resolution. In these patients, daclizumab was only effective in treating skin GVHD. Seven of the nine patients who had a complete or partial response eventually had recurrence of GVHD; however, the GVHD was less severe and no longer corticosteroid refractory. There was no infusional toxicity, and no infections that could be attributable to the drug. Daclizumab is a relatively safe and effective medication for corticosteroid refractory GVHD in children and larger studies are needed to evaluate its role in treatment.
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PMID:Daclizumab for children with corticosteroid refractory graft-versus-host disease. 1624 17

Graft-versus-host disease (GVHD) is caused by alloreactive donor T cells that trigger host tissue injury. GVHD develops over weeks or months, but how this immune response is maintained over time is unknown. In mouse models of human GVHD, we identify a new subset of postmitotic CD44(lo)CD62L(hi)CD8(+) T cells that generate and sustain all allogeneic T-cell subsets in GVHD reactions, including central memory, effector memory and effector CD8(+) T cells, while self-renewing. These cells express Sca-1, CD122 and Bcl-2, and induce GVHD upon transfer into secondary recipients. The postmitotic CD44(lo)CD62L(hi)CD8(+) T cells persist throughout the course of GVHD, are generated in the initial phase in response to alloantigens and dendritic cells and require interleukin-15. Thus, their long life, ability to self-renew and multipotentiality define these cells as candidate memory stem cells. Memory stem cells will be important targets for understanding and influencing diverse chronic immune reactions, including GVHD.
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PMID:Host-reactive CD8+ memory stem cells in graft-versus-host disease. 1633 66

Intestinal transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients who fail total parenteral nutrition (TPN) therapy. Early referral for evaluation for small bowel transplantation has to be considered in patients with permanent intestinal failure who have occlusion of more than two major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation, and is further improving. Rejection, bacterial, fungal and viral (CMV, EBV) infection, post-transplant lymphoproliferative disease (PTLD) and graft versus host disease (GvHD) are the most common complications after intestinal transplantation. Although most of the long-term survivors are TPN-independent and have a good quality of life, the risk of the procedure and long-term adverse effects of immunosuppressive medication limits small bowel, or liver/small bowel transplantation only to patients with severe complications of TPN therapy.
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PMID:Intestinal transplantation in The Netherlands: first experience and future perspectives. 1678 21

Graft-versus-host disease (GVHD) is an uncommon but fatal complication of orthotopic liver transplantation (OLT). The pathogenesis and mechanism of GVHD after OLT remains unclear and the treatment is therefore largely empirical. The prevention of GVHD including avoidance of closely matched human leukocyte antigen donors and old-age recipients is of particular importance because effective treatment is lacking. To reduce immunosuppressants combined with high dose of methylprednisolone and IL-2 receptor antibodies can be applied as a reasonable regime.
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PMID:[Research progress of graft-versus-host disease after liver transplantation]. 1692 14


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