期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 39, 期 10, 页码 2906-2915出版社
WILEY
DOI: 10.1002/eji.200839191
关键词
Cytokine receptors; Cytokines; T cells; Thymus
类别
资金
- Russian Academy of Sciences
- NIH
- National Cancer Institute [N01-CO-12400]
- Deutsches Forschungsgemeinschaft
- European Commission
TNF, lymphotoxin (LT)-alpha, LT-beta 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-, LT beta R- or TNF/LT-deficient backgrounds and of reciprocal bone marrow transfers implicated both LT-alpha/LT-beta to LT beta R and TNF/LT-alpha to TNFR1 signaling in accelerated thymus degeneration. We hypothesize that chronic infections can promote thymic atrophy by upregulating LT and TNF production.
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