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Accelerated thymic atrophy as a result of elevated homeostatic expression of the genes encoded by the TNF/lymphotoxin cytokine locus.
- Source :
- European Journal of Immunology; Oct2009, Vol. 39 Issue 10, p2906-2915, 10p
- Publication Year :
- 2009
-
Abstract
- TNF, lymphotoxin (LT)-α, LT-β and LIGHT are members of a larger superfamily of TNF-related cytokines that can cross-utilize several receptors. Although LIGHT has been implicated in thymic development and function, the role of TNF and LT remains incompletely defined. To address this, we created a model of modest homeostatic overexpression of TNF/LT cytokines using the genomic human TNF/LT locus as a low copy number Tg. Strikingly, expression of Tg TNF/LT gene products led to profound early thymic atrophy characterized by decreased numbers of thymocytes and cortical thymic epithelial cells, partial block of thymocyte proliferation at double negative (DN) 1 stage, increased apoptosis of DN2 thymocytes and severe decline of T-cell numbers in the periphery. Results of backcrossing to TNFR1-, LTβR- or TNF/LT-deficient backgrounds and of reciprocal bone marrow transfers implicated both LT-α/LT-β to LTβR and TNF/LT-α to TNFR1 signaling in accelerated thymus degeneration. We hypothesize that chronic infections can promote thymic atrophy by upregulating LT and TNF production. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00142980
- Volume :
- 39
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- European Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 61988177
- Full Text :
- https://doi.org/10.1002/eji.200839191