Fish requires FasL to facilitate CD8+ T-cell function and antimicrobial immunity

Area of Science:

• Immunology
• Evolutionary Biology
• Fish Biology

Background:

• CD8+ T cells are crucial for adaptive immunity in vertebrates.
• Mechanisms of CD8+ T cell function in bony fish against intracellular pathogens are not well understood.
• Mammalian CD8+ T cells primarily use perforin/granzyme for effector functions.

Purpose of the Study:

• To investigate the function and mechanism of CD8+ T cells in Nile tilapia.
• To elucidate the evolutionary pattern of CD8+ T cell-mediated immunity.
• To explore the role of FasL in fish CD8+ T cell responses.

Main Methods:

• Depletion of CD8+ T cells in Nile tilapia.
• RNA interference (siRNA) to study gene function.
• Analysis of FasL and perforin/granzyme pathways.
• Investigating the mTORC1/c-Myc signaling axis.

Main Results:

• CD8+ T cells are essential for combating Edwardsiella piscicida infection in tilapia.
• Fish CD8+ T cells utilize both FasL and perforin/granzyme for effector functions.
• Tilapia FasL has a dual role: mediating target cell apoptosis and maintaining T cell homeostasis.
• The mTORC1/c-Myc pathway regulates pathogen-induced FasL expression in fish T cells.

Conclusions:

• Fish CD8+ T cells employ a unique dual-function FasL strategy for immunity and homeostasis.
• This study uncovers a novel mechanism of CD8+ T cell function in fish.
• CD8+ T cells have evolved FasL-dependent strategies to enhance adaptive immunity specificity.