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Strong evidence is emerging that the nervous and immune systems share mechanisms of gene regulation, signaling, cell communication, and supracellular organization. This brings to the fore many questions, not least of which is the developmental and evolutionary origin of the commonalities between the two systems. By providing answers to these questions, immunologists and neurobiologists increasingly...
Ikaros family members play an important role in hematopoietic development. Thompson et al. (2007) show that pre-BCR signaling induces Aiolos expression, which in turn suppresses the expression of the pre-BCR component λ5 and eliminates the very structure that signaled its appearance.
The developmental and subset-specific expression of the CD8 genes is under the control of a complex array of regulatory elements distributed along the locus and characterized by DNaseI hypersensitivity. Here we describe the phenotype of mice in which hypersensitive sites 1 and 2 (HSS1 and 2) of DNaseI hypersensitive Cluster II (CII), which are located upstream of the CD8α gene, were deleted by targeted...
The positive selection of CD4 or CD8 single-positive mature peripheral T lymphocytes and the deletion of self-reactive cells are crucial for central tolerance in the peripheral immune system. Previously, the guanine nucleotide binding protein Rac-1 has been shown to control pre-T cell development. The present report now describes the actions of Rac-1 in thymocyte selection. The study reveals that...
The T lymphocyte-specific protein tyrosine kinase p56 lck (Lck) is an essential component of the TCR-mediated signal transduction complex. Lck knockout mice have reduced numbers of double-positive thymocytes and very few mature single-positive cells, particularly of the CD4 lineage. Here we demonstrate the ability of a tetracycline-based tissue-specific inducible Lck transgene to...
CD4 and CD8 are crucial for the development and function of T cells. An intergenic deoxyribonuclease I hypersensitive site region (cluster CIII) directs expression in mature CD8 T cells only. Here, we show that two further independent regions from the CD8 gene locus in conjunction with cluster CIII restore transgene expression in appropriate immature thymocytes. Deletion of two of the intergenic cluster...
The coreceptors CD4 and CD8 play a crucial role during thymocyte development and T cell effector function, and their expression is developmentally regulated. To determine the underlying molecular mechanisms of CD8 gene regulation we cloned the murine CD8 gene locus from genomic libraries and analyzed this region for deoxyribonuclease (DNase I) hypersensitive sites (HSS). Here we report, using transgenic...
The immunodominant epitope of myelin basic protein, Ac1–9, is encephalitogenic in H-2 u mice. We have previously demonstrated that this epitope displays low affinity for I-A u and have suggested that the avidity of T cell recognition in the thymus may be compromised, enabling autoreactive T cells to escape self-tolerance. We have addressed this hypothesis directly by constructing transgenic...
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