Induction of thymocyte positive selection does not convey immediate resistance to negative selection

A molecular chart of thymocyte positive selection.

As a new slant on T lymphocyte repertoire selection, we have examined batteries of TCR sequences in thymi from transgenic mice engineered to exhibit limited, focussed TCR diversity. We have tracked the fate of differentiating thymocytes expressing a set of particular TCR through the positive selection process. Subtly different TCR sequences can promote different maturation pathways and commitme...

DR3 regulates negative selection during thymocyte development.

DR3 (Ws1, Apo3, LARD, TRAMP, TNFSFR12) is a member of the death domain-containing tumor necrosis factor receptor (TNFR) superfamily, members of which mediate a variety of developmental events including the regulation of cell proliferation, differentiation, and apoptosis. We have investigated the in vivo role(s) of DR3 by generating mice congenitally deficient in the expression of the DR3 gene. ...

Negative thymocyte selection to HERV-K18 superantigens in humans.

An experimental system to explore central tolerance in humans is unavailable. However, the human endogenous retrovirus K-18 (HERV-K18) region on chromosome 1 provides an excellent model: HERV-K18 encodes a superantigen (SAg) stimulating Vbeta7CD4 T cells that is implicated in type 1 diabetes and Epstein-Barr virus persistence. In this study, we have addressed thymic HERV-K18 SAg expression, the...

Thymocyte Negative Selection Is Mediated by Protein Kinase C- and Ca -Dependent Transcriptional Induction of Bim

Characteristics of an in vitro system of thymocyte positive selection.

We investigated the phenotypic changes accompanying maturation of CD4+CD8+ thymocytes in the presence of thymic stomal cells in vitro. Many of the features that are characteristic of positive selection in vivo, such as an ordered down-regulation of CD4 or CD8 together with up-regulation of the TCR-alpha beta complex, also occurred in vitro. Transient expression of CD69 was also observed, togeth...