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J Immunol. 2016 Jun 1;196(11):4522-35. doi: 10.4049/jimmunol.1600222. Epub 2016 May 4.

Novel Teleost CD4-Bearing Cell Populations Provide Insights into the Evolutionary Origins and Primordial Roles of CD4+ Lymphocytes and CD4+ Macrophages.

Author information

1
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
2
Virologie et Immunologie Moléculaires, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France;
3
Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Barcelona 08193, Spain; and.
4
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.
5
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; sunyer@vet.upenn.edu.

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.

PMID:
27183628
PMCID:
PMC5100900
DOI:
10.4049/jimmunol.1600222
[Indexed for MEDLINE]
Free PMC Article

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