Natural killer cells prevent CD28-mediated Foxp3 transcription in CD4+CD25– T lymphocytes
| Autor: | Emilie Brillard, Philippe Saas, Xavier Pivot, Pierre Rohrlich, Amandine Radlovic, Jean-René Pallandre, Estelle Seilles, David E. Chalmers, Pierre Tiberghien, Bernhard Ryffel, Christophe Borg |
|---|---|
| Přispěvatelé: | Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2007 |
| Předmět: |
Male
MESH: Antigens CD28 Cancer Research Transcription Genetic MESH: Antigens CD4 Priming (immunology) MESH: Flow Cytometry T-Lymphocytes Regulatory MESH: Mice Knockout Mice Interleukin 21 0302 clinical medicine MESH: Reverse Transcriptase Polymerase Chain Reaction Cytotoxic T cell MESH: Animals IL-2 receptor Cells Cultured Mice Knockout Mice Inbred BALB C 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction CD28 Forkhead Transcription Factors hemic and immune systems Hematology Flow Cytometry Natural killer T cell Adoptive Transfer Cell biology Killer Cells Natural CD4 Antigens Interleukin 12 [SDV.IMM]Life Sciences [q-bio]/Immunology Female MESH: Cells Cultured MESH: Killer Cells Natural MESH: Interferon Type II Transplantation Heterologous MESH: Mice Inbred BALB C chemical and pharmacologic phenomena MESH: Antigens CD45 Biology Interferon-gamma 03 medical and health sciences CD28 Antigens MESH: Lymphocyte Culture Test Mixed MESH: Mice Inbred C57BL MESH: Forkhead Transcription Factors Genetics Animals Humans RNA Messenger MESH: Mice MESH: Transplantation Heterologous Molecular Biology MESH: RNA Messenger 030304 developmental biology MESH: Humans Lymphokine-activated killer cell MESH: T-Lymphocytes Regulatory MESH: Transcription Genetic MESH: Interleukin-2 Cell Biology MESH: Male Mice Inbred C57BL Disease Models Animal MESH: Adoptive Transfer Immunology Interleukin-2 Leukocyte Common Antigens Lymphocyte Culture Test Mixed MESH: Disease Models Animal MESH: Female 030215 immunology |
| Zdroj: | Experimental Hematology Experimental Hematology, Elsevier, 2007, 35 (3), pp.416-25. ⟨10.1016/j.exphem.2006.12.004⟩ |
| ISSN: | 0301-472X |
| DOI: | 10.1016/j.exphem.2006.12.004 |
| Popis: | OBJECTIVE: CD4(+)CD25(+) regulatory T lymphocytes (Treg) have been initially shown to prevent organ-specific autoimmunity. It is now accepted that Treg homeostasis depends in part on the peripheral conversion of na? CD4(+)CD25(-) T cells. This conversion implicates acquisition of the Treg-specific markers, forkhead winged helix protein 3 (Foxp3), after CD28 costimulation. Because natural killer cells (NK) are critical for efficient cytotoxic T-cell priming and TH1 polarization, we investigated their role in Foxp3 induction in CD4(+) T lymphocytes. MATERIALS AND METHODS: Human CD4(+)CD25(-) T lymphocytes were activated in vitro by CD28 costimulation in the presence of interleukin-2-activated NK. Three days after initial activation, Foxp3 protein and RNA expression were determined by flow cytometry and reverse transcription polymerase chain reaction. In vivo influence of activated NK on Foxp3 expression was studied in an adoptive transfer model of CD45.2(+) CD4(+)CD25(-) lymphocytes into CD45.1(+) mice. RESULTS: Interleukin-2-activated NK decreased Treg conversion of adoptively transferred murine CD4(+)CD25(-) T cells in vivo. Likewise, human-activated NK, but not resting NK, decreased CD28-driven Foxp3 expression in CD4(+)CD25(-) T lymphocytes, while at the same time increasing proliferation and interferon-gamma (IFN-gamma) production. Neutralization of IFN-gamma partially restored Treg conversion and prevented TH1 polarization after CD28 costimulation. CONCLUSION: The current study suggests that activated NK interfere with CD28-mediated Foxp3 expression in CD4(+)CD25(-) T lymphocytes. Our experiments further underline a molecular interaction between IFN-gamma and Foxp3 downstream of CD28 signaling. Together, these results demonstrate that activated NK play a critical role at the initiation step of immune responses by modulating peripheral Treg differentiation. |
| Databáze: | OpenAIRE |
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