Wiede, Florian, Roomberg, Alicia, Cretney, Erika , Lechner, Anja, Fromm, Phillip, Wren, Leia, Smyth, Mark J., and Körner, 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.

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Abstract

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-{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.

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