Research from the University of Chicago has revealed a significant role played by certain immune cells in preventing autoimmune diseases. The study, published in Science, offers insights into immune regulation during infections and suggests potential pathways for interventions against autoimmune disorders.
During an infection, the immune system's task is to differentiate between foreign invaders and the body's own molecules. Failure to do so can lead to the immune system attacking its own cells, resulting in tissue damage and chronic diseases.
The research highlights how a specialized group of immune cells acts as "peacekeepers" to prevent other immune cells from mistakenly attacking the body’s own tissues. Professor Pete Savage of UChicago explained that these peacekeeper cells are known as Treg cells, short for CD4+ regulatory T cells. "You can think of them as peacekeeper cells," Savage said.
Dendritic cells are responsible for displaying antigens on their surface after breaking down proteins from pathogens. Helper T cells then inspect these antigens. When dendritic cells present self-peptides instead of foreign ones, Treg cells intervene to stop helper T cells from launching an attack.
Savage's team, led by David Klawon at MIT, explored this mechanism called self-nonself discrimination. Their experiments with mice showed that when Treg cells specific to a self-peptide were removed, helper T cells triggered autoimmunity if infected with bacteria expressing that peptide.
"It's like a doppelganger population of T cells," Savage noted. He added that when they removed specific Treg cells reactive to a self-peptide, the corresponding helper T cells induced autoimmunity.
The study challenges traditional views that suggest purging self-reactive helper T cells is necessary to prevent autoimmunity. Instead, it emphasizes the importance of having matched specificity between helper and regulatory Treg cells.
"The idea is that specificity matters," Savage stated. "For a fully healthy immune system, you need to have a good collection of these doppelganger Treg cells."
This research was conducted in collaboration with Nicole Pagane at MIT and co-authors Harikesh Wong at the Ragon Institute and Ron Germain at NIH. Additional contributors included Matthew Walker and others from UChicago.
The study received funding from several organizations including the National Institute of Allergy and Infectious Diseases and the Chicago Biomedical Consortium.
Citation: "Regulatory T Cells Constrain T Cells of Shared Specificity to Enforce Tolerance During Infection." Klawon et al., Science, Feb. 27, 2025.