The data presented set the stage for investigating both host-specific and virus-specific mechanisms that control primary and sequential DENV infections. Previous immunity is a major risk factor for dengue haemorrhagic fever, so these mice could potentially be used to study the role of cross-reactive sub-neutralizing antibodies and T cells during sequential DENV infections as well as to test drugs and
vaccines against dengue. Increased understanding of the contribution of host components to severe dengue disease MK-2206 manufacturer will lead to the development of effective therapeutics and vaccines. We thank Dr Alan L. Rothman for carefully reading this manuscript and Kim West for technical assistance. This project was supported by grant U19 AI57319 and U19 AI057234 from the National Institute of Allergy and Infectious Diseases, a grant from the Juvenile Diabetes Research Foundation and the Helmsley Foundation,
National Institutes of Health (NIH) grant CA34196, an NIH Diabetes Endocrinology Research Center (DERC) grant DK52530 and support from USAMRID. The authors declare no financial or commercial conflict of interest. “
“Control and termination of infection with Influenza A virus is associated with increased IL-10 production in mouse models. Notably, IL-10 can be produced by Treg. Therefore, we investigated whether the population of IL-10-producing influenza-specific CD4+ Daporinad manufacturer T cells comprised Treg as they are potent suppressors of the adaptive immune response. Influenza-specific IL-10-producing Bumetanide T cells were detected
in all human donors displaying influenza-specific immunity. Isolation of Matrix 1 protein-specific IL-10-producing T-cell clones revealed that a substantial proportion of these T-cell clones displayed the capacity to suppress effector cells, functionally identifying them as Treg. Both FOXP3+ and FOXP3− CD4+ Treg were isolated and all were able to exert their suppressive capacity when stimulated with cognate antigen, including influenza virus-infected cells. In vitro suppression was not mediated by IL-10 but involved interference with the IL-2 axis. The isolated Treg suppressed amongst others the IL-2 production of influenza-specific T-helper cells as well as partially prevented the upregulation of the high-affinity IL-2 receptor on CD8 effector cells. So far the induction of virus-specific Treg has only been studied in the context of chronic viral infections. This study demonstrates that virus-specific Treg can also be induced by viruses that are rapidly cleared in humans. CD4+ Treg can be generated both in the thymus and in the periphery 1. Generation of Treg in the periphery has been well demonstrated in mouse models 2–4. So far, pathogen-specific Treg have been isolated only in the context of chronic infections and viral-induced cancer in humans 5–8 and are thought to be the result of T-cell priming during chronic phases of disease.