Unique phenotype of human tonsillar and in vitro-induced FOXP3+CD8+ T cells
| Autor: | Andreas Speiser, Kerstin Siegmund, Carsten B. Schmidt-Weber, Beate Rückert, Cezmi A. Akdis, Simone Bürgler, Nadia Ouaked |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunology Blotting Western Palatine Tonsil Fluorescent Antibody Technique chemical and pharmacologic phenomena Biology CD8-Positive T-Lymphocytes Lymphocyte Activation Interleukin 21 CD28 Antigens T-Lymphocyte Subsets Immunology and Allergy Cytotoxic T cell Humans IL-2 receptor Antigen-presenting cell Interleukin 3 Reverse Transcriptase Polymerase Chain Reaction ZAP70 Interleukin-2 Receptor alpha Subunit hemic and immune systems Forkhead Transcription Factors Natural killer T cell Flow Cytometry Molecular biology Coculture Techniques Phenotype Interleukin 12 Cytokines |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 182(4) |
| ISSN: | 1550-6606 |
| Popis: | Forkhead box p3 (FOXP3) is known to program the acquisition of suppressive capacities in CD4(+) regulatory T cells (Treg), whereas its role in CD8(+) T cells is unknown. The current study investigates whether FOXP3 also acts as a Treg master switch in peripheral blood and tonsillar CD8(+) T cells. Single-cell analyses reveal the existence of a FOXP3(+)CD8(+) population in human tonsils, whereas FOXP3(+)CD8(+) T cells are rarely detected in peripheral blood. Tonsillar FOXP3(+)CD8(+) T cells exhibit a Treg phenotype with high CTLA-4 and CD45RO and low CD127 and CD69 expression. Interestingly, the tonsillar FOXP3(+)CD8(+) T cells are mostly CD25(negative) and some cells also express the proinflammatory cytokines TNF-alpha, IFN-gamma, or IL-17A. Particularly, IL-17A-expressing cells are present among FOXP3(+)CD8(+) T cells. Even though FOXP3 expression is at the detection limit in peripheral blood CD8(+) T cells ex vivo, it can be induced in vitro in naive CD8(+) T cells by polyclonal stimulation. The induced FOXP3(+)CD8(+) T cells are predominantly CD25(high) and CD28(high) and similar to tonsillar cells, they produce high levels of TNF-alpha, IFN-gamma, and granzyme B. However, IL-4 expression is mutually exclusive and IL-17A expression is not detectable. These FOXP3(+)CD8(+) T cells suppress the proliferation of CD4(+) T cells in cocultures, while showing no direct cytotoxic activity. In conclusion, the current study characterizes FOXP3-expressing CD8(+) T cells from human tonsils and shows that in vitro activation leads to FOXP3 expression in CD8(+) T cells and gain of suppressive activity. |
| Databáze: | OpenAIRE |
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