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Age-dependent, polyclonal hyperactivation of T cells is reduced in TNF-negative gld/gld mice
journal contribution
posted on 2023-05-17, 07:48 authored by Wiede, F, Roomberg, A, Cretney, E, Lechner, A, Fromm, P, Wren, L, Smyth, MJ, Heinrich KornerHeinrich KornerThe 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.
History
Publication title
Journal of Leukocyte BiologyVolume
85Pagination
108-116ISSN
0741-5400Department/School
Menzies Institute for Medical ResearchPublisher
Federation Amer Soc Exp BiolPlace of publication
9650 Rockville Pike, Bethesda, USA, Md, 20814-3998Repository Status
- Restricted