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Natural killer cells prevent CD28-mediated Foxp3 transcription in CD4+CD25- T lymphocytes.
Exp Hematol 2007; 35(3):416-25EH

Abstract

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 naïve 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.

Authors+Show Affiliations

INSERM U645, University of Franche Comté, EFS Bourgogne Franche Comté, Besançon, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17309822

Citation

Brillard, Emilie, et al. "Natural Killer Cells Prevent CD28-mediated Foxp3 Transcription in CD4+CD25- T Lymphocytes." Experimental Hematology, vol. 35, no. 3, 2007, pp. 416-25.
Brillard E, Pallandre JR, Chalmers D, et al. Natural killer cells prevent CD28-mediated Foxp3 transcription in CD4+CD25- T lymphocytes. Exp Hematol. 2007;35(3):416-25.
Brillard, E., Pallandre, J. R., Chalmers, D., Ryffel, B., Radlovic, A., Seilles, E., ... Borg, C. (2007). Natural killer cells prevent CD28-mediated Foxp3 transcription in CD4+CD25- T lymphocytes. Experimental Hematology, 35(3), pp. 416-25.
Brillard E, et al. Natural Killer Cells Prevent CD28-mediated Foxp3 Transcription in CD4+CD25- T Lymphocytes. Exp Hematol. 2007;35(3):416-25. PubMed PMID: 17309822.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Natural killer cells prevent CD28-mediated Foxp3 transcription in CD4+CD25- T lymphocytes. AU - Brillard,Emilie, AU - Pallandre,Jean-René, AU - Chalmers,David, AU - Ryffel,Bernhard, AU - Radlovic,Amandine, AU - Seilles,Estelle, AU - Rohrlich,Pierre Simon, AU - Pivot,Xavier, AU - Tiberghien,Pierre, AU - Saas,Philippe, AU - Borg,Christophe, PY - 2006/08/15/received PY - 2006/12/06/revised PY - 2006/12/11/accepted PY - 2007/2/21/pubmed PY - 2007/12/13/medline PY - 2007/2/21/entrez SP - 416 EP - 25 JF - Experimental hematology JO - Exp. Hematol. VL - 35 IS - 3 N2 - 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 naïve 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. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/17309822/Natural_killer_cells_prevent_CD28_mediated_Foxp3_transcription_in_CD4+CD25__T_lymphocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-472X(06)00747-8 DB - PRIME DP - Unbound Medicine ER -