Age-dependent, polyclonal hyperactivation of T cells is reduced in TNF-negativegld/gldmice
| Autor: | Phillip D. Fromm, Leia Wren, Florian Wiede, Heinrich Körner, Erika Cretney, Anja Lechner, Alicia Roomberg, Mark J. Smyth |
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| Rok vydání: | 2008 |
| Předmět: |
Aging
Receptors CCR7 medicine.medical_specialty T cell Immunology Mice Transgenic Spleen C-C chemokine receptor type 7 Biology Lymphocyte Activation medicine.disease_cause Fas ligand Autoimmunity Interferon-gamma Mice T-Lymphocyte Subsets Internal medicine medicine Animals Immunology and Allergy L-Selectin Receptor Lymphatic Diseases Cell Proliferation Tumor Necrosis Factor-alpha Cell Differentiation Cell Biology Lymphoproliferative Disorders Mice Inbred C57BL Hyaluronan Receptors medicine.anatomical_structure Endocrinology Splenomegaly biology.protein Tumor necrosis factor alpha Lymph Nodes Antibody |
| Zdroj: | Journal of Leukocyte Biology. 85:108-116 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | The generalized lymphoproliferative disorder (gld) mouse strain is characterized by severe splenomegaly/lymphadenopathy, the production of autoimmune antibodies, and the appearance of CD4/CD8-negative T cells. An additional TNF deficiency of gld/gld mice attenuates the course of the disorder through a yet-unknown mechanism. In this study, we could demonstrate that the reduced splenomegaly and lymphadenopathy in B6.gld/gld.TNF−/− mice were correlated with a decreased peripheral T cell proliferation rate and a delayed polyclonal activation. A comparative analysis of naïve T cells and memory/effector T cells showed an age-dependent difference in the T cell activation pattern in the spleen of B6.gld/gld and B6.gld/gld.TNF−/− mice. T cells from B6.gld/gld.TNF−/− spleens and lymph nodes showed significantly higher levels of CCR7 and CD62 ligand on their surface compared with B6.gld/gld mice when mice of the same age were compared. Additionally, we found an increased titer of the Th1 cytokine IFN-γ in the serum of B6.gld/gld mice, whereas the concentration of IFN-γ was markedly reduced in the serum of B6.gld/gld.TNF−/− mice. These findings support the hypothesis that increased T cell activation and proliferation in the presence of TNF contribute to the exacerbation of the gld syndrome. |
| Databáze: | OpenAIRE |
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