The cytokine networks of adaptive immunity in fish

• Cytokines are key regulators of the immune system.
• CD4+ T-helper (Th) cells play an important role in orchestrating adaptive immune responses.
• Th1, Th2, Th17 and induced T-regulatory cells have been characterized in mammals.
• Increasing molecular and cellular evidence suggests the existence of Th cells in fish.
• Alternative or additional Th populations may also exist in fish.

Cytokines, produced at the site of entry of a pathogen, drive inflammatory signals that regulate the capacity of resident and newly arrived phagocytes to destroy the invading pathogen. They also regulate antigen presenting cells (APCs), and their migration to lymph nodes to initiate the adaptive immune response. When naive CD4+ T cells recognize a foreign antigen-derived peptide presented in the context of major histocompatibility complex class II on APCs, they undergo massive proliferation and differentiation into at least four different T-helper (Th) cell subsets (Th1, Th2, Th17, and induced T-regulatory (iTreg) cells in mammals. Each cell subset expresses a unique set of signature cytokines. The profile and magnitude of cytokines produced in response to invasion of a foreign organism or to other danger signals by activated CD4+ T cells themselves, and/or other cell types during the course of differentiation, define to a large extent whether subsequent immune responses will have beneficial or detrimental effects to the host. The major players of the cytokine network of adaptive immunity in fish are described in this review with a focus on the salmonid cytokine network. We highlight the molecular, and increasing cellular, evidence for the existence of T-helper cells in fish. Whether these cells will match exactly to the mammalian paradigm remains to be seen, but the early evidence suggests that there will be many similarities to known subsets. Alternative or additional Th populations may also exist in fish, perhaps influenced by the types of pathogen encountered by a particular species and/or fish group. These Th cells are crucial for eliciting disease resistance post-vaccination, and hopefully will help resolve some of the difficulties in producing efficacious vaccines to certain fish diseases.