Insights into the dynamics of memory, effector and apoptotic cytotoxic T Lymphocytes in channel catfish, Ictalurus punctatus

Authors: SPENCER, DAVID - Oregon Health & Science University; Quiniou, Sylvie; CRIDER, JONATHAN - University Of Mississippi Medical Center; Musungu, Bryan; BENTEN, EVA - University Of Mississippi Medical Center; WILSON, MELANIE - University Of Mississippi Medical Center

Submitted to: Developmental and Comparative Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/14/2018
Publication Date: 3/1/2019
Citation: Spencer, D.A., Quiniou, S., Crider, J., Musungu, B.M., Benten, E., Wilson, M. 2019. Insights into the dynamics of memory, effector and apoptotic cytotoxic T Lymphocytes in channel catfish, Ictalurus punctatus. Developmental and Comparative Immunology. 92:116-128.

Interpretive Summary: Cytotoxic T cells are critical elements of the immune response to pathogens or cancers. They recognize cells invaded by pathogens or abnormal cells such as cancerous cells and kill them to avoid spreading of pathogens or cancers. In this study we characterize how a model catfish cytotoxic cell line TS32.15 reacts when exposed to abnormal cells. When exposed to target the small cytotoxic T cells will multiply and change morphology to become big, granular and able to kill targets. Once their job is done they lose the ability to kill and die. This information helps understand how the catfish immune system eliminates pathogens, the mechanisms involved in disease resistance in fish and how to design better vaccines to protect fish.

Technical Abstract: In this study, we used the channel catfish model clonal TS32.15 alloantigen-specific cytotoxic T cell (CTL) line, to examine the dynamics of memory CTL expansion and senescence in teleosts. Although TS32.15 has been routinely cultured to study catfish CTL responses and killing mechanisms, little is known about the dynamics of the CTLs in these cultures. Here we show that this cell line consists of small non-cytotoxic T cells and larger granular effector T cells and that their ratios vary with time after stimulation. Small CTLs, when exposed to their irradiated targets, replicate and differentiate to morphologically distinct cytotoxic effectors, which do not replicate. After lysing target cells, or with prolonged absence of stimulation, the effector cells transition to a non-cytolytic senescent stage or become apoptotic. In addition, we demonstrate that natural IgM in catfish serum, binds lipids including PIP2 on early apoptotic CTLs and that these IgM+ CTL can be cleared by catfish head kidney derived macrophages.