The Pathogenesis of Schistosomiasis Is Controlled by Cooperating IL-10-Producing Innate Effector and Regulatory T Cells

• Published in: The Journal of immunology (1950) 2004-03, Vol.172 (5), p.3157-3166
• Main Authors: Hesse, Matthias, Piccirillo, Ciriaco A, Belkaid, Yasmine, Prufer, Jeannette, Mentink-Kane, Margaret, Leusink, Mary, Cheever, Allen W, Shevach, Ethan M, Wynn, Thomas A
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antigens, Helminth - immunology; CD25 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - transplantation; Cells, Cultured; Cytokines - biosynthesis; Female; Immunity, Innate - genetics; Interleukin-10 - biosynthesis; Interleukin-10 - deficiency; Interleukin-10 - genetics; Liver - immunology; Liver - metabolism; Liver - pathology; Liver Diseases, Parasitic - immunology; Liver Diseases, Parasitic - pathology; Liver Diseases, Parasitic - prevention & control; Mice; Mice, Inbred C57BL; Mice, Knockout; Morbidity; Ovum - immunology; RAG2 gene; Receptors, Interleukin-2 - biosynthesis; Schistosomiasis mansoni - genetics; Schistosomiasis mansoni - immunology; Schistosomiasis mansoni - mortality; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.5.3157

IL-10 reduces immunopathology in many persistent infections, yet the contribution of IL-10 from distinct cellular sources remains poorly defined. We generated IL-10/recombination-activating gene (RAG)2-deficient mice and dissected the role of T cell- and non-T cell-derived IL-10 in schistosomiasis by performing adoptive transfers. In this study, we show that IL-10 is generated by both the innate and adaptive immune response following infection, with both sources regulating the development of type-2 immunity, immune-mediated pathology, and survival of the infected host. Importantly, most of the CD4(+) T cell-produced IL-10 was confined to a subset of T cells expressing CD25. These cells were isolated from egg-induced granulomas and exhibited potent suppressive activity in vitro. Nevertheless, when naive, naturally occurring CD4(+)CD25(+) cells were depleted in adoptive transfers, recipient IL-10/RAG2-deficient animals were more susceptible than RAG2-deficient mice, confirming an additional host-protective role for non-T cell-derived IL-10. Thus, innate effectors and regulatory T cells producing IL-10 cooperate to reduce morbidity and prolong survival in schistosomiasis.