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

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 defence. The innate and adaptive arms of the vertebrate immune system collaborate to mount an effective defence 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.