AUTHOR=Shao Tong , Shi Wei , Zheng Jia-yu , Xu Xiao-xiao , Lin Ai-fu , Xiang Li-xin , Shao Jian-zhong 

TITLE=Costimulatory Function of Cd58/Cd2 Interaction in Adaptive Humoral Immunity in a Zebrafish Model

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01204

DOI=10.3389/fimmu.2018.01204

ISSN=1664-3224

ABSTRACT=<p>CD58 and CD2 have long been known as a pair of reciprocal adhesion molecules involved in the immune modulations of CD8<sup>+</sup> T and NK-mediated cellular immunity in humans and several other mammals. However, the functional roles of CD58 and CD2 in CD4<sup>+</sup> T-mediated adaptive humoral immunity remain poorly defined. Moreover, the current functional observations of CD58 and CD2 were mainly acquired from <italic>in vitro</italic> assays, and <italic>in vivo</italic> investigation is greatly limited due to the absence of a <italic>Cd58</italic> homology in murine models. In this study, we identified <italic>cd58</italic> and <italic>cd2</italic> homologs from the model species zebrafish (<italic>Danio rerio</italic>). These two molecules share conserved structural features to their mammalian counterparts. Functionally, <italic>cd58</italic> and <italic>cd2</italic> were significantly upregulated on antigen-presenting cells and Cd4<sup>+</sup> T cells upon antigen stimulation. Blockade or knockdown of Cd58 and Cd2 dramatically impaired the activation of antigen-specific Cd4<sup>+</sup> T and mIgM<sup>+</sup> B cells, followed by the inhibition of antibody production and host defense against bacterial infections. These results indicate that CD58/CD2 interaction was required for the full activation of CD4<sup>+</sup> T-mediated adaptive humoral immunity. The interaction of Cd58 with Cd2 was confirmed by co-immunoprecipitation and functional competitive assays by introducing a soluble Cd2 protein. This study highlights a new costimulatory mechanism underlying the regulatory network of adaptive immunity and makes zebrafish an attractive model organism for the investigation of CD58/CD2-mediated immunology and disorders. It also provides a cross-species understanding of the evolutionary history of costimulatory signals from fish to mammals as a whole.</p>