Immunoglobulin-like transcript 3-Fc suppresses T-cell responses to allogeneic human islet transplants in hu-NOD/SCID mice.
Objective: The aim of our study was to explore the immunomodulatory activity of soluble immunoglobulin (Ig)-like transcript (ILT) 3-Fc in pancreatic islet transplantation and to determine its mechanism of action.Research Design and Methods: NOD/SCID mice in which diabetes was induced by streptozotoc...
| Publicado en: | Diabetes Vol. 57; no. 7; pp. 1878 - 1887 |
|---|---|
| Autores principales: | , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
American Diabetes Association
Jul2008
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105786424&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105786424 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00121797 1G6 jtl: Diabetes issn: 00121797 maglogo: N pubinfo: dt: Jul2008 vid: 57 iid: 7 pid: 1367 pub: American Diabetes Association place: Arlington, Virginia artinfo: ui: 105786424 105786424 NLM18420485 2009983211 10.2337/db08-0054 NLM18420485 105786424 ppf: 1878 ppct: 9 formats: tig: atl: Immunoglobulin-like transcript 3-Fc suppresses T-cell responses to allogeneic human islet transplants in hu-NOD/SCID mice. aug: au: Vlad G D'Agati VD Zhang QY Liu Z Ho EK Mohanakumar T Hardy MA Cortesini R Suciu-Foca N Vlad, George D'Agati, Vivette D Zhang, Qing-Yin Liu, Zhuoru Ho, Eric K Mohanakumar, Thalachallour Hardy, Mark A Cortesini, Raffaello Suciu-Foca, Nicole affil: Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York, USA sug: subj: Diabetes Mellitus Surgery Islets of Langerhans Transplantation Receptors, Cell Surface Immunology T Lymphocytes Immunology Xenografts Allografts Animals Diabetes Mellitus Immunology Female Glycoproteins Graft Rejection Immunoglobulin Fragments Immunology Immunoglobulin Fragments Therapeutic Use Immunoglobulin Fragments Immunoglobulins Immunology Mice Polymerase Chain Reaction Receptors, Cell Surface Therapeutic Use Receptors, Cell Surface RNA Female ab: Objective: The aim of our study was to explore the immunomodulatory activity of soluble immunoglobulin (Ig)-like transcript (ILT) 3-Fc in pancreatic islet transplantation and to determine its mechanism of action.Research Design and Methods: NOD/SCID mice in which diabetes was induced by streptozotocin injection were transplanted with human pancreatic islet cells. Mice in which the transplant restored euglycemia were humanized with allogeneic peripheral blood mononuclear cells and treated with ILT3-Fc or control human IgG or left untreated. The blood glucose level was monitored twice a week, and rejection was diagnosed after two consecutive readings >350 mg/dl. Tolerated and rejected grafts were studied histologically and by immunostaining for human T-cells and insulin production. CD4 and CD8 T-cells from the spleen were studied for suppressor activity, expression of cytokines, and CD40L.Results: Although human T-cell engraftment was similar in all groups, ILT3-Fc-treated mice tolerated the islets for the entire period of observation (91 days), whereas control mice rejected the graft within 7 weeks (P < 0.0001). ILT3-Fc treatment suppressed the expression of cytokines and CD40L and induced the differentiation of human CD8(+) T suppressor cells that inhibited Th alloreactivity against graft HLA antigens. T-cells allostimulated in vitro in the presence of ILT3-Fc inhibited CD40L-induced upregulation of CD40 in human pancreatic islet cells. Histochemical studies showed dramatic differences between human pancreatic islets from tolerant, ILT3-Fc-treated mice and control recipients rejecting the grafts.Conclusions: The data indicated that ILT3-Fc is a potent immunoregulatory agent that suppressed islet allograft rejection in humanized NOD/SCID mice. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|