Advanced Course in Immunology On Demand Lecture Recordings-T Cell Tolerance and Autoimmunity

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Video Summary

The speaker gave a broad overview of T-cell tolerance, explaining how the immune system distinguishes self from non-self and avoids attacking the body’s own tissues. He framed tolerance as a multilayered balance between immune activation and restraint, involving central tolerance in the thymus and peripheral tolerance in the body.<br /><br />Historically, he described early cow and mouse graft experiments that showed tolerance is an active, antigen-specific process, work that helped establish the field and earned Billingham, Brent, and Medawar the Nobel Prize. In the thymus, immature T cells that strongly recognize self-antigen are deleted, while some CD4 T cells become regulatory T cells (Tregs). He highlighted the role of the AIRE gene, which drives expression of many tissue-specific self-antigens in thymic epithelial cells, allowing developing T cells to be “educated” against self. Mutations in AIRE cause severe multiorgan autoimmunity.<br /><br />In peripheral tolerance, the speaker emphasized the need for both antigen recognition and co-stimulation for full T-cell activation. Molecules such as CD28 stimulate responses, while CTLA-4 and PD-1 act as inhibitory checkpoints. These pathways are central to preventing autoimmunity but are also targeted in cancer immunotherapy, where blocking them can unleash anti-tumor immunity at the cost of autoimmune side effects. Other mechanisms discussed included activation-induced cell death and suppression by FOXP3+ Tregs.<br /><br />The talk then shifted to autoimmunity, covering genetic risk factors, especially HLA/MHC, as well as environmental triggers like infection, hormones, and possibly microbial exposure. The speaker concluded that the long-term goal is antigen-specific tolerance therapies—especially via Tregs—that would suppress harmful autoimmunity while preserving normal immunity.

Asset Subtitle

Lecture 15: Mark S. Anderson, University of California, San Francisco, School of Medicine

T Cell Tolerance and Autoimmunity

Asset Caption

Mark S. Anderson, University of California, San Francisco, School of Medicine
T Cell Tolerance and Autoimmunity

Keywords

T-cell tolerance

immune self-recognition

central tolerance

peripheral tolerance

thymus

AIRE gene

regulatory T cells

CTLA-4

PD-1

autoimmunity

HLA/MHC

cancer immunotherapy