Wiede, Florian and Roomberg, Alicia and Cretney, Erika and Lechner, Anja and Fromm, Phillip and Wren, Leia and Smyth, Mark J. and Korner, Heinrich (2009) Age-dependent, polyclonal hyperactivation of T cells is reduced in TNF-negative gld/gld mice. JOURNAL OF LEUKOCYTE BIOLOGY, 85 (1). pp. 108-116. ISSN 0741-5400, 1938-3673
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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 naive 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-gamma in the serum of B6.gld/gld mice, whereas the concentration of IFN-gamma 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. J. Leukoc. Biol. 85: 108-116; 2009.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; GENERALIZED LYMPHOPROLIFERATIVE DISORDER; MRL-LPR/LPR MICE; LPR MICE; FAS-LIGAND; AUTOIMMUNE-DISEASE; LYMPHOID ORGANS; DENDRITIC CELLS; FACTOR RECEPTOR; EXPRESSION; autoimmunity; knockout mice; tumor necrosis factor; Fas ligand |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Oct 2020 14:05 |
| Last Modified: | 13 Oct 2020 14:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29773 |
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