A lymphotoxin-IFN-beta axis essential for lymphocyte survival revealed during cytomegalovirus infection
| Autor: | Won Ha, Theresa A. Banks, Stefanie Scheu, Dirk Elewaut, Kirsten Schneider, Dennis C. Otero, Lisa Ma, Olga Turovskaya, Stanley C. Henry, Steven W. Granger, Joshua Meier, Carl F. Ware, John D. Hamilton, Mira Ko, Anthony R. French, Klaus Pfeffer, Chris A. Benedict, Sandra Rickert |
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| Rok vydání: | 2005 |
| Předmět: |
Agonist
Lymphotoxin-beta Muromegalovirus Tumor Necrosis Factor Ligand Superfamily Member 14 Stromal cell medicine.drug_class Cell Survival Lymphocyte medicine.medical_treatment Immunology Apoptosis Mice Transgenic Receptor Interferon alpha-beta Biology Receptors Tumor Necrosis Factor Mice Lymphotoxin beta Receptor Lymphopenia medicine Immunology and Allergy Animals Humans Lymphotoxin-alpha Receptors Interferon Mice Knockout Immunity Cellular Tumor Necrosis Factor-alpha Membrane Proteins Immunotherapy Herpesviridae Infections Interferon-beta Lymphocyte Subsets Mice Inbred C57BL Haematopoiesis Lymphatic system medicine.anatomical_structure Lymphotoxin Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0022-1767 |
| Popis: | The importance of lymphotoxin (LT) βR (LTβR) as a regulator of lymphoid organogenesis is well established, but its role in host defense has yet to be fully defined. In this study, we report that mice deficient in LTβR signaling were highly susceptible to infection with murine CMV (MCMV) and early during infection exhibited a catastrophic loss of T and B lymphocytes, although the majority of lymphocytes were themselves not directly infected. Moreover, bone marrow chimeras revealed that lymphocyte survival required LTα expression by hemopoietic cells, independent of developmental defects in lymphoid tissue, whereas LTβR expression by both stromal and hemopoietic cells was needed to prevent apoptosis. The induction of IFN-β was also severely impaired in MCMV-infected LTα−/− mice, but immunotherapy with an agonist LTβR Ab restored IFN-β levels, prevented lymphocyte death, and enhanced the survival of these mice. IFN-αβR−/− mice were also found to exhibit profound lymphocyte death during MCMV infection, thus providing a potential mechanistic link between type 1 IFN induction and lymphocyte survival through a LTαβ-dependent pathway important for MCMV host defense. |
| Databáze: | OpenAIRE |
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