Article

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

Comparative Genomics Centre, School of Veterinary and Biomedical Science/School of Pharmacy and Molecular Sciences, Molecular Sciences Bldg. 21, James Cook University, Townsville, Qld 4811, Australia.
Journal of Leukocyte Biology (impact factor: 4.99). 11/2008; 85(1):108-16. DOI:10.1189/jlb.0107018 pp.108-16
Source: PubMed

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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Keywords

additional TNF deficiency
 
age-dependent difference
 
B6.gld/gld mice
 
B6.gld/gld.TNF-/- mice
 
B6.gld/gld.TNF-/- spleens
 
CD4/CD8-negative T cells
 
comparative analysis
 
decreased peripheral T cell proliferation rate
 
delayed polyclonal activation
 
findings support
 
generalized lymphoproliferative disorder
 
gld syndrome
 
gld/gld mice attenuates
 
increased T cell activation
 
lymph nodes
 
memory/effector T cells
 
naïve T cells
 
T cell activation pattern
 
T cells
 
Th1 cytokine IFN-gamma