| First Author | Wiede F | Year | 2009 |
| Journal | J Leukoc Biol | Volume | 85 |
| Issue | 1 | Pages | 108-16 |
| PubMed ID | 18948547 | Mgi Jnum | J:144623 |
| Mgi Id | MGI:3831442 | Doi | 10.1189/jlb.0107018 |
| Citation | Wiede F, et al. (2009) Age-dependent, polyclonal hyperactivation of T cells is reduced in TNF-negative gld/gld mice. J Leukoc Biol 85(1):108-16 |
| abstractText | 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. |
