Negligible Role for Deletion Mediated by cDC1 in CD8⁺ T Cell Tolerance

Area of Science:

• Immunology
• Cell Biology
• T cell immunology

Background:

• Dendritic cells (DCs) are crucial for immune tolerance by deleting self-reactive T cells.
• Peripheral deletion of autoreactive CD8+ T cells by DCs is known for model antigens.
• The role of DCs in shaping the natural CD8+ T cell repertoire remains unclear.

Purpose of the Study:

• To investigate the role of cross-presenting CD8α+ and CD103+ DCs (cDC1) in peripheral deletion of CD8+ T cells.
• To determine if cDC1 influence the self-reactivity of the endogenous CD8+ T cell repertoire.
• To assess the impact of cDC1 on shaping the naturally occurring polyclonal CD8+ T cell repertoire.

Main Methods:

• Utilized Batf3-deficient mice, which lack cDC1.
• Studied CD8+ T cell deletion in response to a model tissue antigen.
• Performed deep T cell receptor (TCR) sequencing of peripheral CD8+ T cells.

Main Results:

• Peripheral deletion of CD8+ T cells reactive to a model tissue antigen was dependent on cDC1.
• CD8+ T cells from Batf3 mice did not show increased self-reactivity.
• Deep TCR sequencing revealed a minimal impact of cDC1 on shaping the peripheral CD8+ T cell repertoire.

Conclusions:

• While cDC1 mediate deletion of CD8+ T cells in specific models, their role in maintaining tolerance to natural self-ligands is negligible.
• cDC1 have a minimal influence on the composition of the natural peripheral CD8+ T cell repertoire.
• Immune tolerance to self-antigens may involve mechanisms beyond cDC1-mediated deletion of polyclonal CD8+ T cells.