Enhanced T-cell activation and effector functions contribute to disease resistance in Streptococcus agalactiae-resistant tilapia

To address the considerable challenges posed by frequent Streptococcus agalactiae infections in tilapia aquaculture, we previously developed a strain of tilapia with enhanced resistance to this pathogen. Understanding the immune mechanisms behind this resistance is essential for advancing selective breeding strategies. This study concentrates on T-cell activation and effector function to explore the reasons for the more robust immunity in S. agalactiae-resistant tilapia. Through RNA-seq and immunological assays, we demonstrated that resistant tilapia possessed a higher proportion of T cells and enhanced T-cell effector functions compared to susceptible tilapia. Upon in vitro stimulation with anti-tilapia CD3ε plus CD28 monoclonal antibodies (mAbs), or in vivo infection with S. agalactiae, spleen leukocytes from resistant tilapia showed significantly enhanced degrees of Erk1/2 and NF-κB p65 phosphorylation, which are classical signaling pathway of T-cell activation. Once activated, spleen lymphocytes from resistant tilapia expressed higher levels of inflammatory cytokines, such as TNF-α, IL-2, as well as cytotoxic molecule perforin A. Moreover, CD4–1⁺ T cells in the resistant tilapia produced greater amounts of interferon (IFN)-γ, suggesting their superior T-cell effector functions. These findings collectively illustrate how enhanced T-cell activation and effector responses facilitate the optimized immune defenses of resistant tilapia. By shedding light on these mechanisms, our findings provide a valuable foundation for refining breeding programs aimed at increasing disease resistance in aquaculture.