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-␥ 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 cytokine networks of adaptive immunity in fish

“…A few B7 family members have been identified recently in fish and are able to induce IL-2 expression. For example, the fugu B7-H3 or B7-H4 Ig fusion proteins induce IL-2 expression in T-cell enriched cultures in the presence of PHA [13]. A trout CD80/86 like molecule also upregulates the expression of IL-2 in trout blood leucocytes [11].…”

The cytosolic sensor, DDX41, activates antiviral and inflammatory immunity in response to stimulation with double-stranded DNA adherent cells of the olive flounder, Paralichthys olivaceus

“…PBLs (peripheral blood leukocytes) and KLs (whole kidney leukocytes) were isolated from peripheral blood and whole kidney, respectively, by Percoll (GE Healthcare, Little Chalfont, UK) density gradient (1.065 and 1.050 g ml À1 ) centrifugation at 1500 rpm for 50 min at 4 C. After centrifugation, the PBLs and KLs were removed, washed three times with HBSS, and resuspended in L-15 medium supplemented with 5% FBS and 1% penicillin/streptomycin. Monocyte-like cells were isolated as previously described [20]. Briefly, PBLs and KLs were incubated for 1 h in a flask (TPP Techno Plastic Products) that had been pretreated with heat-inactivated olive flounder serum at 34 C for1 h. Following incubation, the lymphocyte-enriched supernatant was carefully collected.…”

Molecular characterization and expression of CD2 in Nile tilapia (Oreochromis niloticus) in response to Streptococcus agalactiae stimulus

“…In mammals, CD2 can function as a costimulatory molecule and accelerate production of IL-2, which is the most important cytokine to promote proliferation and differentiation of T-cells [11e15]. Recent progress in evolutionary immunology supports the notion that the capacity to modulate IL-2 expression is a primordial function that has been conserved in both fish and mammals costimulatory molecules [39,41,69], suggesting On-CD2 may also possess similar function to activate T-cells. This hypothesis was supported by distinct kinetic expressions of On-CD2 in the thymus and spleen.…”