Influenza matrix 1-specific human CD4+ FOXP3+ and FOXP3(-) regulatory T cells can be detected long after viral clearance.
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(+) 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(+) 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.
Piersma
Sytse J
SJ
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
van der Hulst
Jeanette M
JM
Kwappenberg
Kitty M C
KM
Goedemans
Renske
R
van der Minne
Caroline E
CE
van der Burg
Sjoerd H
SH
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D009980:Influenza A virus / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508594:IL2 protein, human; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014763:Viral Matrix Proteins; D016753:Interleukin-10