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| Item Type: | Article |
|---|---|
| Title: | CCR6 is expressed on an IL-10–producing, autoreactive memory T cell population with context-dependent regulatory function |
| Creators Name: | Rivino, L., Gruarin, P., Häringer, B., Steinfelder, S., Lozza, L., Steckel, B., Weick, A., Sugliano, E., Jarrossay, D., Kühl, A.A., Loddenkemper, C., Abrignani, S., Sallusto, F., Lanzavecchia, A. and Geginat, J. |
| Abstract: | Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10-producing memory T cells. Human CD4(+)CCR6(+) memory T cells contained comparable numbers of IL-17- and IL-10-producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic T cell priming with transforming growth factor (TGF)-beta. In normal human spleens, the majority of CCR6(+) memory T cells were in the close vicinity of CCR6(+) myeloid dendritic cells (mDCs), and strikingly, some of them were secreting IL-10 in situ. Furthermore, CCR6(+) memory T cells produced suppressive IL-10 but not IL-2 upon stimulation with autologous immature mDCs ex vivo, and secreted IL-10 efficiently in response to suboptimal T cell receptor (TCR) stimulation with anti-CD3 antibodies. However, optimal TCR stimulation of CCR6(+) T cells induced expression of IL-2, interferon-gamma, CCL20, and CD40L, and autoreactive CCR6(+) T cell lines responded to various recall antigens. Notably, we isolated autoreactive CCR6(+) T cell clones with context-dependent behavior that produced IL-10 with autologous mDCs alone, but that secreted IL-2 and proliferated upon stimulation with tetanus toxoid. We propose the novel concept that a population of memory T cells, which is fully equipped to participate in secondary immune responses upon recognition of a relevant recall antigen, contributes to the maintenance of tolerance under steady-state conditions. |
| Keywords: | CCR6 Receptors, CD4-Positive T-Lymphocytes, Gene Expression Regulation, Homeostasis, Immunologic Memory, Immunosuppression Therapy, Interferon-gamma, Interleukin-10, Interleukin-2, Regulatory T-Lymphocytes, T-Cell Antigen Receptors, T-Lymphocytes, Transforming Growth Factor Beta |
| Source: | Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Volume: | 207 |
| Number: | 3 |
| Page Range: | 565-577 |
| Date: | 15 March 2010 |
| Official Publication: | https://doi.org/10.1084/jem.20091021 |
| PubMed: | View item in PubMed |
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