A Signal Integration Model of Thymic Selection and Natural Regulatory T Cell Commitment

A Signal Integration Model of Thymic

T-cell lineage commitment and cytokine responses of thymic progenitors.

The earliest steps of intrathymic differentiation recently have been elucidated. It has been reported that both CD4lo (CD44+ CD25- c-kit+ CD3- CD4lo CD8-) and pro-T cells (CD44+ CD25+ c-kit+ CD3- CD4- CD8-, representing the next step in maturation) exhibit germline T-cell receptor beta and gamma loci, suggesting that neither population is exclusively committed to the T-cell lineage. Several gro...

A20 Restrains Thymic Regulatory T Cell Development

Maintaining immune tolerance requires the production of Foxp3-expressing regulatory T (Treg) cells in the thymus. Activation of NF-κB transcription factors is critically required for Treg cell development, partly via initiating Foxp3 expression. NF-κB activation is controlled by a negative feedback regulation through the ubiquitin editing enzyme A20, which reduces proinflammatory signaling in m...

Thymic T-Cell Education: Positive & Negative Selection

TOLERANCE (which is antigen-specific) must be distinguished from immune deficiency (non-specific). Its most important manifestation, the maintenance of SELFTOLERANCE, was originally explained by the Clonal Selection theory as the result of CLONAL ABORTION of self-reactive clones. However, potentially self-reactive Tand B-cells do exist in normal individuals, leading to the recognition of the im...

Molecular signature of recent thymic selection events on effector and regulatory CD4 T lymphocytes Running title: Thymic selection of effector and regulatory CD4 T lymphocytes

Natural CD4CD25 regulatory T lymphocytes are key protagonists in induction and maintenance of peripheral T cell tolerance. Their thymic origin and biased repertoire continue to raise important questions on the signals that mediate their development. We validated analysis of MHC class II-capture by developing thymocytes from thymic stroma as a tool to study quantitative and qualitative aspects o...