CD4+ T lymphocyte responses to viruses and virus-relevant stimuli in teleost fish

Authors: BELA-ONG, DENNIS - Gyeongsang National University; THOMPSON, KIM - The Moredun Group; KIM, HYOUNG - National Research Institute Of Fisheries Science, Fisheries Research Agency; PARK, SEONGBIN - Mississippi State University; JUNG, TAE - Gyeongsang National University

Submitted to: Fish and Shellfish Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/17/2023
Publication Date: 10/4/2023
Citation: Bela-Ong, D.B., Thompson, K., Kim, H.J., Park, S., Jung, T.S. 2023. CD4+ T lymphocyte responses to viruses and virus-relevant stimuli in teleost fish. Fish and Shellfish Immunology. 142:109007. https://doi.org/10.1016/j.fsi.2023.109007.
DOI: https://doi.org/10.1016/j.fsi.2023.109007

Interpretive Summary: Fish diseases caused by viruses are a major threat to aquaculture. To develop effective protection strategies, it's essential to understand fish immune mechanisms, especially their antiviral defenses. The immune system has two parts, innate and adaptive, which work together to fight viruses. In the adaptive system, T lymphocytes (CD4+ helper T cells and CD8+ cytotoxic T cells) play a crucial role. Antibodies to CD4 and transcription profiling reveal T helper (Th) cell responses to viral stimuli in fish. Fish CD4+ T cells, found in fish too, are key in coordinating immune responses. Fish Th cells proliferate and express signature molecules upon stimulation. Fish CD4+ T cell responses are reminiscent of Th cell responses in mammals. However, current understanding of teleost Th cell responses is far from complete. Conventional and new tools/approaches will be keys to fully understand fish Th cell responses. Improving our knowledge could help combat viral infections in fish farming and use fish as models to study immune responses.

Technical Abstract: Fish diseases caused by viruses are a major threat to aquaculture. Development of disease protection strategies for sustainable fish aquaculture requires a better understanding of the immune mechanisms involved in antiviral defense. The innate and adaptive arms of the vertebrate immune system collaborate to mount an effective defense against viral pathogens. The T lymphocyte components of the adaptive immune system, comprising two major classes (helper T, Th or CD4+ and cytotoxic T lymphocytes, CTLs or CD8+ T cells), are responsible for cell-mediated immune responses. In particular, CD4+ T cells and their different subsets orchestrate the actions of various other immune cells during immune responses, making CD4+ T cells central drivers of responses to pathogens and vaccines. CD4+ T cells are also present in teleost fish. Here we review the literature that reported the use of antibodies against CD4 in a few teleost fish species and transcription profiling of Th cell-relevant genes in the context of viral infections and virus-relevant immunomodulation. Studies reveal massive CD4+ T cell proliferation and expression of key cytokines, transcription factors, and effector molecules that evoke mammalian Th cell responses. We also discuss gaps in the current understanding and evaluation of teleost CD4+ T cell responses and how development and application of novel tools and approaches to interrogate such responses could bridge these gaps. A greater understanding of fish Th cell responses will further illuminate the evolution of vertebrate adaptive immunity, inform strategies to address viral infections in aquaculture, and could further foster fish as model organisms.