Negative Selection in the Thymus Includes Semimature T Cells

Negative Selection in the Thymus Includes Semimature T Cells

The thymic medulla plays a key role in negative selection (self-tolerance induction) and contains differentiated T cells en route to the extrathymic environment. However, being relatively mature, medullary T cells are thought to be beyond the stage of tolerance induction. This paradox is resolved by the finding that medullary T cells (CD4+8- thymocytes) comprise two distinct subsets. Medullary ...

Elimination of Self-Reactive T Cells in the Thymus: A Timeline for Negative Selection

The elimination of autoreactive T cells occurs via thymocyte apoptosis and removal by thymic phagocytes, but the sequence of events in vivo, and the relationship between thymocyte death and phagocytic clearance, are unknown. Here we address these questions by following a synchronized cohort of thymocytes undergoing negative selection within a three-dimensional thymic tissue environment, from th...

Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus

Transplantation of bone marrow cells of lpr/lpr mice into irradiated normal mice fails to develop massive lymphadenopathy or autoimmunity but causes severe graft-vs.-host-like syndrome. To elucidate an abnormality of lpr/lpr bone marrow-derived T cells, we transplanted bone marrow cells of Mlsb lpr/lpr mice into H-2-compatible Mlsa non-lpr mice. Although lpr/lpr T cell precursors repopulated th...

Proving negative selection in the thymus.

Generation of CD4(+)CD25(+) regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from nonautoreactive T cells by endogenous TCR expression.

Normal T cell repertoire contains regulatory T cells that control autoimmune responses in the periphery. One recent study demonstrated that CD4(+)CD25(+) T cells were generated from autoreactive T cells without negative selection. However, it is unclear whether, in general, positive selection and negative selection of autoreactive T cells are mutually exclusive processes in the thymus. To inves...