Slc43a2⁺ T cell metastasis from spleen to brain in RGNNV infected teleost

The origin of T cells in the teleost’s brain is unclear. While viewing the central nervous system (CNS) as immune privileged has been widely accepted, previous studies suggest that T cells residing in the thymus but not in the spleen of the teleost play an essential role in communicating with the peripheral organs. Here, we identified nine T cell subpopulations in the thymus and spleen of orange-spotted grouper (Epinephelus coioices) through single-cell RNA-sequencing analysis. After viral CNS infection with red-spotted grouper nervous necrosis virus (RGNNV), the number of slc43a2⁺ T cells synchronously increased in the spleen and brain. During the infection tests in asplenic zebrafish (tlx1^▲ zebrafish model), no increase in the number of slc43a2⁺ T cells was observed in the brain. Single-cell transcriptomic analysis indicated that slc43a2⁺ T cells mature and functionally differentiate within the spleen and then migrate into the brain to trigger an immune response. This study suggests a novel route for T cell migration from the spleen to the brain during viral infection in fish.