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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lai, Laijun Jin, Jingjun Hodio, Jennifer Goldschneider, Irving |
| Description | Country affiliation: United States Author Affiliation: Lai L ( Department of Immunology, School of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. llai@neuron.uchc.edu) |
| Abstract | BACKGROUND: T-cell regeneration after bone marrow transplantation (BMT) is often slow and incomplete. Therefore, the enhancement of T-cell reconstitution after BMT is required. We have previously described a naturally occurring hybrid cytokine consisting of interleukin (IL)-7 and the ß-chain of hepatocyte growth factor (HGF) that had lymphopoietic stimulatory activity in vitro. We have also reported that a murine recombinant (r) IL-7/HGFß protein significantly enhances T-cell regeneration in mice after BMT. METHODS: To determine whether a human form of rIL-7/HGFß has similar effects as the murine form, we have cloned and expressed the human IL-7 and HGFß genes to produce a single-chain hrIL-7/HGFß protein. We have also cloned and expressed a human form of hybrid cytokine containing IL-7 and the -chain of HGF (HGF ) (hrIL-7/HGF ). We then determined their ability to enhance T-cell reconstitution in mice after BMT. RESULTS: We found that hrIL-7/HGF had higher in vitro and in vivo thymocyte-stimulatory activities than did the hrIL-7/HGFß. Therefore, we focused on the functional properties of hrIL-7/HGF and showed that administration of hrIL-7/HGF significantly enhanced thymopoiesis in mice after syngeneic BMT by increasing the numbers of thymocytes, early thymocyte progenitors, and thymic epithelial cells. hrIL-7/HGF cross-linked the IL-7 and HGF receptors on thymocytes, and the in vivo thymocyte-stimulatory activity was mediated by both receptors. Consequently, hrIL-7/HGF treatment significantly increased the numbers of total and naïve T cells in the periphery. CONCLUSION: In vivo administration of hrIL-7/HGF efficiently restores thymopoiesis and naïve T-cell reconstitution in mice after syngeneic BMT. |
| File Format | HTM / HTML |
| ISSN | 00411337 |
| Issue Number | 5 |
| Volume Number | 92 |
| e-ISSN | 15346080 |
| Journal | Transplantation Journal |
| Language | English |
| Publisher | Lippincott Williams & Wilkins |
| Publisher Date | 2011-09-15 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Transplantation Bone Marrow Transplantation Immunology Hepatocyte Growth Factor Pharmacology Interleukin-7 T-lymphocytes Drug Effects Animals Genetics Humans Lymphocyte Count Lymphopoiesis Mice Mice, Inbred C57bl Proto-oncogene Proteins C-met Metabolism Receptors, Antigen, T-cell Receptors, Interleukin-7 Recombinant Fusion Proteins T-lymphocyte Subsets Cytology Transplantation, Isogeneic Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Transplantation |
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