Cutting edge: generation of effector cells that localize to mucosal tissues and form resident memory CD8 T cells is...

Area of Science:

• Immunology
• Cellular Biology
• Infectious Disease

Background:

• Mucosal tissues are primary sites for pathogen entry and infectious disease transmission.
• CD8 T cells are crucial for controlling infections acquired at mucosal sites, but their migration is regulated.
• The mechanisms governing tissue-resident memory CD8 T cell formation are not fully understood.

Purpose of the Study:

• To investigate the role of mammalian target of rapamycin (mTOR) in the formation of tissue-resident memory CD8 T cells in mucosal tissues.
• To determine the impact of rapamycin, an mTOR inhibitor, on CD8 T cell populations in the gut and vagina.
• To assess the therapeutic potential of modulating mTOR signaling in mucosal CD8 T cell-mediated immunity and autoimmunity.

Main Methods:

• Treatment of mice with rapamycin to inhibit mammalian target of rapamycin kinase.
• Analysis of CD8 T cell populations in secondary lymphoid tissues and mucosal sites (intestinal, vaginal).
• Evaluation of CD8 T cell-mediated intestinal autoimmunity models in mice.

Main Results:

• Rapamycin enhanced the formation of memory CD8 T cells in secondary lymphoid tissues.
• Conversely, rapamycin inhibited the development of resident memory CD8 T cells in the intestinal and vaginal mucosa.
• Blocking resident CD8 T cell formation in the mucosa using rapamycin conferred protection against lethal intestinal autoimmunity.

Conclusions:

• Mammalian target of rapamycin (mTOR) plays opposing roles in the generation of resident versus non-resident CD8 T cell immunity.
• Inhibition of mTOR signaling can selectively impair mucosal resident memory CD8 T cell formation.
• Targeting mTOR may offer a strategy to control CD8 T cell-mediated mucosal immunity and associated autoimmune diseases.