Glutamine Metabolism Underlies the Functional Similarity of T Cells between Nile Tilapia and Tetrapod

Abstract

As the lowest organisms possessing T cells, fish are instrumental for understanding T cell evolution and immune defense in early vertebrates. This study established in Nile tilapia models suggests that T cells play a critical role in resisting Edwardsiella piscicida infection via cytotoxicity and are essential for IgM+ B cell response. CD3 and CD28 monoclonal antibody crosslinking reveals that full activation of tilapia T cells requires the first and secondary signals, while Ca2+–NFAT, MAPK/ERK, NF‐κB, and mTORC1 pathways and IgM+ B cells collectively regulate T cell activation. Thus, despite the large evolutionary distance, tilapia and mammals such as mice and humans exhibit similar T cell functions. Furthermore, it is speculated that transcriptional networks and metabolic reprogramming, especially c‐Myc‐mediated glutamine metabolism triggered by mTORC1 and MAPK/ERK pathways, underlie the functional similarity of T cells between tilapia and mammals. Notably, tilapia, frogs, chickens, and mice utilize the same mechanisms to facilitate glutaminolysis‐regulated T cell responses, and restoration of the glutaminolysis pathway using tilapia components rescues the immunodeficiency of human Jurkat T cells. Thus, this study provides a comprehensive picture of T cell immunity in tilapia, sheds novel perspectives for understanding T cell evolution, and offers potential avenues for intervening in human immunodeficiency.

Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals

“…The spleen leukocytes (3×10 6 ) were cultured in a 24-well plate with DMEM containing 10% FBS and 1% penicillin/streptomycin (Sangon Biotech, China) at 28 °C. The cells were then stimulated with previously generated CD3ε and CD28 mAbs (2 μg/mL) ( Li et al, 2023 ), and collected at indicated times for assay. Unstimulated leukocytes were used for the control.…”