Cutting edge : membrane lymphotoxin regulates CD8(+) T cell-mediated intestinal allograft rejection
Blocking the CD28/B7 and/or CD154/CD40 costimulatory pathways promotes long-term allograft survival in many transplant models where CD4(+) T cells are necessary for rejection. When CD8(+) T cells are sufficient to mediate rejection, these approaches fail, resulting in costimulation blockade-resistant rejection. To address this problem we examined the role of lymphotoxin-related molecules in CD8(+) T cell-mediated rejection of murine intestinal allografts. Targeting membrane lymphotoxin by means of a fusion protein, mAb, or genetic mutation inhibited rejection of intestinal allografts by CD8(+) T cells. This effect was associated with decreased monokine induced by IFN-gamma (Mig) and secondary lymphoid chemokine (SLC) gene expression within allografts and spleens respectively. Blocking membrane lymphotoxin did not inhibit rejection mediated by CD4(+) T cells. Combining disruption of membrane lymphotoxin and treatment with CTLA4-Ig inhibited rejection in wild-type mice. These data demonstrate that membrane lymphotoxin is an important regulatory molecule for CD8(+) T cells mediating rejection and suggest a strategy to avoid costimulation blockade-resistant rejection.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2001 |
|---|---|
| Erschienen: |
2001 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:167 |
|---|---|
| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 167(2001), 9 vom: 01. Nov., Seite 4796-800 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guo, Z [VerfasserIn] |
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| Anmerkungen: |
Date Completed 05.12.2001 Date Revised 15.05.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM115681701 |
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| 041 | |a eng | ||
| 100 | 1 | |a Guo, Z |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cutting edge |b membrane lymphotoxin regulates CD8(+) T cell-mediated intestinal allograft rejection |
| 264 | 1 | |c 2001 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 05.12.2001 | ||
| 500 | |a Date Revised 15.05.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Blocking the CD28/B7 and/or CD154/CD40 costimulatory pathways promotes long-term allograft survival in many transplant models where CD4(+) T cells are necessary for rejection. When CD8(+) T cells are sufficient to mediate rejection, these approaches fail, resulting in costimulation blockade-resistant rejection. To address this problem we examined the role of lymphotoxin-related molecules in CD8(+) T cell-mediated rejection of murine intestinal allografts. Targeting membrane lymphotoxin by means of a fusion protein, mAb, or genetic mutation inhibited rejection of intestinal allografts by CD8(+) T cells. This effect was associated with decreased monokine induced by IFN-gamma (Mig) and secondary lymphoid chemokine (SLC) gene expression within allografts and spleens respectively. Blocking membrane lymphotoxin did not inhibit rejection mediated by CD4(+) T cells. Combining disruption of membrane lymphotoxin and treatment with CTLA4-Ig inhibited rejection in wild-type mice. These data demonstrate that membrane lymphotoxin is an important regulatory molecule for CD8(+) T cells mediating rejection and suggest a strategy to avoid costimulation blockade-resistant rejection | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Antigens, CD |2 NLM | |
| 650 | 7 | |a Antigens, Differentiation |2 NLM | |
| 650 | 7 | |a CTLA-4 Antigen |2 NLM | |
| 650 | 7 | |a Ctla4 protein, mouse |2 NLM | |
| 650 | 7 | |a Immunoconjugates |2 NLM | |
| 650 | 7 | |a Lymphotoxin-alpha |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Tumor Necrosis Factor |2 NLM | |
| 650 | 7 | |a Receptors, Tumor Necrosis Factor, Member 14 |2 NLM | |
| 650 | 7 | |a Receptors, Virus |2 NLM | |
| 650 | 7 | |a Tnfrsf14 protein, mouse |2 NLM | |
| 650 | 7 | |a Tnfsf14 protein, mouse |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor Ligand Superfamily Member 14 |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
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| 700 | 1 | |a Wang, J |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, L |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Q |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, O |e verfasserin |4 aut | |
| 700 | 1 | |a Hart, J |e verfasserin |4 aut | |
| 700 | 1 | |a He, G |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, P |e verfasserin |4 aut | |
| 700 | 1 | |a Thistlethwaite, J R |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Alegre, M L |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Y X |e verfasserin |4 aut | |
| 700 | 1 | |a Newell, K A |e verfasserin |4 aut | |
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