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- Carow, B, et al.
(author)
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lck-Driven Cre Expression Alters T Cell Development in the Thymus and the Frequencies and Functions of Peripheral T Cell Subsets
- 2016
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 197:6, s. 2261-2268
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Journal article (peer-reviewed)abstract
- Conditional gene targeting using the bacteriophage-derived Cre recombinase is widely applied for functional gene studies in mice. Mice transgenic for Cre under the control of the lck gene promoter are used to study the role of loxP-targeted genes in T cell development and function. In this article, we show a striking 65% reduction in cellularity, preferential development of γδ versus αβ T cells, and increased expression of IL-7R in the thymus of mice expressing Cre under the proximal lck promoter (lck-cre+ mice). The transition from CD4/CD8 double-negative to double-positive cells was blocked, and lck-cre+ double-positive cells were more prone to apoptosis and showed higher levels of Cre expression. Importantly, numbers of naive T cells were reduced in spleens and lymph nodes of lck-cre+ mice. In contrast, frequencies of γδ T cells, CD44+CD62L− effector T cells, and Foxp3+ regulatory T cells were elevated, as was the frequency of IFN-γ–secreting CD4+ and CD8+ T cells. A literature survey of 332 articles that used lck-cre+ mice for deletion of floxed genes indicated that results are statistically influenced by the control used (lck-cre+ or lck-cre−), more frequently resembling the lck-cre+ phenotype described in this article if lck-cre− controls were used. Altogether, care should be taken when interpreting published results and to properly control targeted gene deletions using the lck-cre+ strain.
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- Liu, RN, et al.
(author)
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HIF-1 stabilization in T cells hampers the control of Mycobacterium tuberculosis infection
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 5093-
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Journal article (peer-reviewed)abstract
- The hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection withM. tuberculosisisn’t well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection withM. tuberculosis, which is associated with a low accumulation of mycobacteria-specific T cells in the lungs that display reduced proliferation, altered differentiation and enhanced expression of inhibitory receptors. In contrast, HIF-1 deficiency in T cells is redundant forM. tuberculosiscontrol.Vhl cKOmice also show reduced responses to vaccination. Further, VHL promotes proper MYC-activation, cell-growth responses, DNA synthesis, proliferation and survival of CD4 T cells after TCR activation. The VHL-deficient T cell responses are rescued by the loss of HIF-1α, indicating that the increased susceptibility toM. tuberculosisinfection and the impaired responses ofVhl-deficient T cells are HIF-1-dependent.
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