Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine Journal Article
| Authors: | Waldman, E.; Lu, S. X.; Hubbard, V. M.; Kochman, A. A.; Eng, J. M.; Terwey, T. H.; Muriglan, S. J.; Kim, T. D.; Heller, G.; Murphy, G. F.; Liu, C.; Alpdogan, O.; van den Brink, M. R. M. |
| Article Title: | Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine |
| Abstract: | The α4β7 integrin plays a central role in the homing of T cells to the gut. We hypothesized that absence of the β7 subunit would result in a reduction of intestinal graft-versus-host disease (GVHD) and an improvement in overall GVHD morbidity and mortality in recipients of hematopoietic stem cell transplantation (HSCT). Analysis of alloreactive β7-/- T cells showed intact activation, proliferation, cytokine production, and cytotoxicity. However, recipients of β7-/- donor T cells in murine HSCT models experienced less GVHD morbidity and mortality than recipients of wild-type (WT) T cells, associated with a decrease in donor T-cell infiltration of the liver and intestine and with an overall significant decrease in hepatic and intestinal GVHD. In graft-versus-tumor (GVT) experiments, we demonstrated intact or even enhanced GVT activity of β7-/- donor T cells. In conclusion, β7-/- donor T cells caused less GVHD morbidity and mortality than WT donor T cells because of selectively decreased T-cell infiltration of the liver and intestines. Our data suggest that strategies to target the β7 integrin have the clinical potential to alleviate or prevent GVHD while sparing or potentiating GVT activity. © 2006 by The American Society of Hematology. |
| Keywords: | gene deletion; genetics; mortality; nonhuman; cell proliferation; t lymphocyte; t-lymphocytes; animal cell; mouse; animal; animals; mice; animal tissue; cell infiltration; morbidity; animal experiment; animal model; hematopoietic stem cell transplantation; cytotoxicity; wild type; enzyme linked immunosorbent assay; mice, inbred c57bl; c57bl mouse; disease model; cytokine; liver; immunology; graft versus host reaction; liver disease; cytokine production; cytotoxicity, immunologic; enzyme-linked immunosorbent assay; disease models, animal; graft vs host disease; cell activation; graft versus leukemia effect; enteropathy; intestine; alloimmunity; recipient; mastocytoma; beta7 integrin; integrin beta chains; immunity, mucosal; mice, inbred dba; mucosal immunity; beta integrin; dba mouse |
| Journal Title: | Blood |
| Volume: | 107 |
| Issue: | 4 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2006-02-15 |
| Start Page: | 1703 |
| End Page: | 1711 |
| Language: | English |
| DOI: | 10.1182/blood-2005-08-3445 |
| PUBMED: | 16291587 |
| PROVIDER: | scopus |
| PMCID: | PMC1895413 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 30" - "Export Date: 4 June 2012" - "CODEN: BLOOA" - "Source: Scopus" |
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