Influenza matrix 1-specific human CD4 super(+)FOXP3 super(+) and FOXP3 super(-) regulatory T cells can be detected long after viral clearance

• Published in: European journal of immunology 2010-11, Vol.40 (11), p.3064-3074
• Main Authors: Piersma, Sytse J, van der Hulst, Jeanette M, Kwappenberg, Kitty MC, Goedemans, Renske, van der Minne, Caroline E, van der Burg, Sjoerd H
• Format: Article
• Language: English
• Subjects: Influenza A virus; Orthomyxoviridae
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200940177

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 super(+) T cells comprised Treg as they are potent suppressors of the adaptive immune response. Influenza-specific IL-10-producing 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 super(+) and FOXP3 super(-) CD4 super(+) 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.