Teleost B7 Expressed on Monocytes Regulates T Cell Responses

Abstract

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-γ 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.