Advanced Course in Immunology On Demand Lecture Recordings-T Cell Development

Video Transcription

Video Summary

The lecture gave an overview of T cell development in the thymus, emphasizing how stem-cell precursors from the bone marrow are guided into the T cell lineage and matured into functional CD4 and CD8 T cells. The speaker explained the thymic stages from double-negative to double-positive to single-positive cells, using flow cytometry markers and developmental gene programs to show how these populations are identified.<br /><br />A major focus was the role of NOTCH signaling, which promotes thymocyte survival, proliferation, and commitment to the T cell lineage. The talk also covered T cell receptor generation through V(D)J recombination, including the roles of RAG1/2 and TdT, and how receptor expression shuts down further rearrangement once a functional receptor is made.<br /><br />The thymic environment was highlighted as essential for selection. Cortical thymic epithelial cells support positive selection, while medullary thymic epithelial cells, using AIRE and FEZF2, expose developing T cells to tissue-specific self-antigens for negative selection, preventing autoimmunity. The speaker also discussed MHC restriction: T cells only recognize antigen when presented by the appropriate self-MHC molecule.<br /><br />Another key point was the development of specialized T cell subsets, including gamma delta T cells, invariant NKT cells, MAIT cells, and FOXP3-positive regulatory T cells, which contribute to rapid immune responses and tolerance.<br /><br />The lecture concluded with a discussion of thymic involution with age, reduced T cell output in older individuals, and implications for vaccination, infection, cancer, and immune competence.

Asset Subtitle

Lecture 10: Avery August, Cornell University

T Cell Development

Asset Caption

Avery August, Cornell University
T Cell Development

Keywords

T cell development

thymus

thymocyte maturation

NOTCH signaling

V(D)J recombination

RAG1/2

TdT

positive selection

negative selection

MHC restriction

regulatory T cells

thymic involution