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Age-dependent, polyclonal hyperactivation of T cells is reduced in TNF-negative gld/gld mice
journal contributionposted on 2023-05-17, 07:48 authored by Wiede, F, Roomberg, A, Cretney, E, Lechner, A, Fromm, P, Wren, L, Smyth, MJ, Heinrich KornerHeinrich Korner
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 naÃ¯ve 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-Î³ in the serum of B6.gld/gld mice, whereas the concentration of IFN-Î³ 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. Â© Society for Leukocyte Biology.
Publication titleJournal of Leukocyte Biology
Department/SchoolMenzies Institute for Medical Research
PublisherFederation Amer Soc Exp Biol
Place of publication9650 Rockville Pike, Bethesda, USA, Md, 20814-3998