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Teleost B7 Expressed on Monocytes Regulates T Cell Responses^1,2

Fisheries Laboratory, Graduate School of Agricultural and Life Sciences, University of Tokyo, Hamamatsu, Japan

In mammals, professional APCs induce adaptive immunity via the activation of T cells. During this process, B7 family molecules present upon APCs are known to play crucial roles in optimal T cell stimulation. In contrast, the confirmation of APCs in a nonmammalian vertebrate has yet to be achieved. To obtain further insights into the evolutionary origin of APCs, we have identified three members of the B7 family in the teleost Takifugu rubripes (fugu): B7-H1/DC, B7-H3, and B7-H4. The three fugu B7s were expressed on the surface of blood monocytes. The B7⁺ monocytes, which are composed of at least two distinct populations, expressed the MHC class II component gene. The fugu B7 molecules bound to activated T cells, indicating that putative B7 receptors were expressed upon T cells. Fugu B7-H1/DC inhibited T cell proliferation concomitant with increasing levels of both IL-10 and IFN- expression, whereas both B7-H3 and B7-H4 promoted T cell growth following IL-2 induction and the suppression of IL-10. These observations indicate that fugu B7s regulate T cell responses via receptors upon T cells. We suggest that fish B7⁺ monocytes are APCs and that a costimulatory system has already developed in fish via the evolutionary process.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by Grant-in-Aid for Scientific Research from Ministry of Education, Culture, Sports Science, and Technology of Japan.

² The sequences presented in this article have been submitted to GenBank under accession numbers AB453016 (fugu B7-H1/DC); AF317088 (mouse B7-H1; version AF317088.1); NM_021396 (mouse B7-DC); AB453017 (fugu B7-H3); NM_001024736 (human 4IgB7-H3); NM_133983 (mouse B7-H3, version NM-); AB453018 (fugu B7-H4); AY280973 (mouse B7-H4; version AY280973.1); X60958 (mouse B7-1); BC013807 (mouse B7-2); and NM_015790 (mouse B7-H2).

³ Address correspondence and reprint requests to Dr. Hiroaki Suetake, Fisheries Laboratory, Graduate School of Agricultural and Life Sciences, University of Tokyo, 2971-4 Maisaka, Hamamatsu, Shizuoka 431-0214, Japan. E-mail address: asuetake{at}mail.ecc.u-tokyo.ac.jp

⁴ Abbreviations used in this paper: DC, dendritic cell; BLAST, basic local alignment search tool; EF, elongation factor.

⁵ The online version of this article contains supplemental material.