T-Cell Development Overview

Early stage of T cell development in the thymus where thymocytes lack both CD4 and CD8 markers.

The stage in T-cell development where thymocytes express both CD4 and CD8 markers.

The stage in T-cell development where thymocytes express either CD4 or CD8 marker, but not both.

A signaling pathway crucial for committing thymocytes to the T-cell lineage.

A receptor on developing thymocytes that provides survival signals, ensuring their viability.

A receptor on early thymocytes that promotes proliferation by interacting with stem cell factor (SCF).

The process where a thymocyte interacts with MHC molecules presenting self-antigens with low affinity, ensuring the ability to recognize self-MHC.

The process where thymocytes that bind strongly to self-antigens presented by MHC molecules are eliminated, protecting against autoimmunity.

A transcription factor that controls expression of self-antigens in medullary thymic epithelial cells (mTECs), facilitating negative selection and promoting tolerance.

A model of T-cell selection that focuses on the strength of TCR-MHC interactions, with low affinity favoring positive selection and high affinity leading to negative selection.

T cells are essential for adaptive immunity; they identify and respond to pathogens while maintaining self-tolerance. Their development occurs in the thymus, a vital primary lymphoid organ.

Hematopoietic stem cells (HSCs) from bone marrow migrate to the thymus where they transform into mature T cells within 2-3 weeks. This process involves a series of developmental stages and is essential for generating a diverse population of T cells.

Jacques Miller's thymectomy experiments in neonatal mice revealed the thymus's crucial role in immunity. Removing the thymus led to reduced lymphocyte counts, impaired graft rejection, and deficient antibody responses, highlighting the thymus's vital contribution to immune function.

Thymic atrophy, the gradual replacement of thymic tissue with fat, occurs with age. This leads to a decline in thymic output, meaning fewer new T cells are produced. However, immune competence persists in adults due to the longevity and self-renewal capacity of existing T cells.

The thymus is divided into two distinct regions: the cortex and the medulla.

The cortex of the thymus is the site of early T-cell development. Cortical epithelial cells provide essential signals for thymocyte proliferation and positive selection, ensuring only T cells with the potential to recognize foreign antigens survive.

The medulla of the thymus is where later stages of T-cell development and self-tolerance mechanisms occur. Medullary epithelial cells (mTECs) express self-antigens, enabling negative selection—eliminating T cells that could attack the body's own tissues.

T-cell development involves three main stages based on the expression of CD4 and CD8 surface markers: double-negative (DN), double-positive (DP), and single-positive (SP).