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Age-dependent, polyclonal hyperactivation of T cells is reduced in TNF-negative gld/gld mice


Wiede, F and Roomberg, A and Cretney, E and Lechner, A and Fromm, P and Wren, L and Smyth, MJ and Korner, H, 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 (2009) [Refereed Article]

DOI: doi:10.1189/jlb.0107018


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. © Society for Leukocyte Biology.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Korner, H (Professor Heinrich Korner)
ID Code:72558
Year Published:2009
Web of Science® Times Cited:7
Deposited By:Research Division
Deposited On:2011-08-29
Last Modified:2011-08-29

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