Macrophages treated with antigen from the tapeworm Hymenolepis diminuta condition CD25 + T cells to suppress colitis.

Macrophages play central roles in immunity as early effectors and modulating adaptive immune reponses; we implicated macrophages in the anticolitic effect of infection with the tapeworm Hymenolepis diminuta. Here, gene arrays revealed that H. diminuta antigen (HdAg) evoked a program in murine macrophages distinct from that elicited by IL-4. Further, HdAg suppressed LPS-evoked release of TNF-α and IL-1β from macrophages via autocrine IL-10 signaling. In assessing the ability of macrophages treated in vitro with an extract of H. diminuta [M ^(HdAg) ] to affect disease, intravenous, but not peritoneal, injection of M ^(HdAg) protected wild-type but not RAG1 ^-/- mice from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Administration of splenic CD4 ⁺ T cells from in vitro cocultures with M ^(HdAg) , but not those cocultured with M ^(IL-4) cells, inhibited DNBS-induced colitis; fractionation of the T-cell population indicated that the CD4 ⁺ CD25 ⁺ T cells from cocultures with M ^(HdAg) drove the suppression of DNBS-induced colitis. Use of IL-4 ^-/- or IL-10 ^-/- CD4 ⁺ T cells revealed that neither cytokine alone from the donor cells was essential for the anticolitic effect. These data illustrate that HdAg evokes a unique regulatory program in macrophages, identifies HdAg-evoked IL-10 suppression of macrophage activation, and reveals the ability of HdAg-treated macrophages to educate ( i.e., condition) and mobilize CD4 ⁺ CD25 ⁺ T cells, which could be deployed to treat colonic inflammation.-Reyes, J. L., Lopes, F., Leung, G., Jayme, T. S., Matisz, C. E., Shute, A., Burkhard, R., Carneiro, M., Workentine, M. L., Wang, A., Petri, B., Beck, P. L., Geuking, M. B., McKay, D. M., Macrophages treated with antigen from the tapeworm Hymenolepis diminuta condition CD25 ⁺ T cells to suppress colitis.