title: Novel Teleost CD4-Bearing Cell Populations Provide Insights into the Evolutionary Origins and Primordial Roles of CD4+ Lymphocytes and CD4+ Macrophages.
abstract: Tetrapods contain a single CD4 coreceptor with four Ig domains that likely arose from a primordial two-domain ancestor. Notably, teleost fish contain two CD4 genes. Like tetrapod CD4, CD4-1 of rainbow trout includes four Ig domains, whereas CD4-2 contains only two. Because CD4-2 is reminiscent of the prototypic two-domain CD4 coreceptor, we hypothesized that by characterizing the cell types bearing CD4-1 and CD4-2, we would shed light into the evolution and primordial roles of CD4-bearing cells. Using newly established mAbs against CD4-1 and CD4-2, we identified two bona-fide CD4(+) T cell populations: a predominant lymphocyte population coexpressing surface CD4-1 and CD4-2 (CD4 double-positive [DP]), and a minor subset expressing only CD4-2 (CD4-2 single-positive [SP]). Although both subsets produced equivalent levels of Th1, Th17, and regulatory T cell cytokines upon bacterial infection, CD4-2 SP lymphocytes were less proliferative and displayed a more restricted TCRβ repertoire. These data suggest that CD4-2 SP cells represent a functionally distinct population and may embody a vestigial CD4(+) T cell subset, the roles of which reflect those of primeval CD4(+) T cells. Importantly, we also describe the first CD4(+) monocyte/macrophage population in a nonmammalian species. Of all myeloid subsets, we found the CD4(+) population to be the most phagocytic, whereas CD4(+) lymphocytes lacked this capacity. This study fills in an important gap in the knowledge of teleost CD4-bearing leukocytes, thus revealing critical insights into the evolutionary origins and primordial roles of CD4(+) lymphocytes and CD4(+) monocytes/macrophages.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Fumio
authors.identifier: 0000-0002-0988-2770
authors.initials: F
authors.lastname: Takizawa
authors.affiliation: Virologie et Immunologie Moléculaires, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France;
authors.forename: Susana
authors.identifier: 0000-0003-2968-0102
authors.initials: S
authors.lastname: Magadan
authors.affiliation: Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Barcelona 08193, Spain; and.
authors.forename: David
authors.identifier: 0000-0002-3634-7087
authors.initials: D
authors.lastname: Parra
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agriculture University, Wuhan, Hubei 430070, China.
authors.forename: Zhen
authors.identifier: 0000-0001-6598-2058
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Tomáš
authors.initials: T
authors.lastname: Korytář
authors.affiliation: Virologie et Immunologie Moléculaires, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France;
authors.forename: Pierre
authors.initials: P
authors.lastname: Boudinot
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; sunyer@vet.upenn.edu.
authors.forename: J Oriol
authors.initials: JO
authors.lastname: Sunyer
mesh_terms: D000818:Animals; D005075:Biological Evolution; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology*; D017686:Oncorhynchus mykiss / Q000276:immunology*
chemical_list: D015704:CD4 Antigens