NKG2D is an activating receptor expressed on CD8(+)alpha beta(+) T cells, alpha beta(+) T cells, natural killer (NK) cells, and some CD4(+) T cells. For a long time, the interaction of NKG2D with its ligands (NKG2DLs) MICA, MICB, and ULBP1-3 has been considered a mechanism for recognition and elimination of tumor, infected, or otherwise "stressed" cells. However, a new role for NKG2D as an immunoregulatory receptor is emerging. Here, we show that NKG2D is strongly down-modulated on antigen-activated CD8(+) T cells but only if CD4(+) T cells are present. Down-modulation was caused by soluble factors produced by CD4(+) T cells, and in particular soluble NKG2DLs were found in the supernatants of antigen-activated T-cell cultures. MICB was the ligand released at higher levels when CD4(+) T cells were present in the cell cultures, suggesting that it could be the major player of NKG2D down-modulation. CD8(+) T cells expressing low levels of NKG2D had impaired effector functions, as evaluated by proliferation, cytokine production, and cytotoxicity assays after combined triggering of NKG2D and TCR-CD3 complex. These findings show that activated CD4(+) T cells expressing NKG2DLs can efficiently prevent NKG2D-mediated CD8(+) T-cell functions, and suggest that the NKG2D/NKG2DL interaction can regulate immune responses. (Blood. 2009; 113: 2955-2964)

Detuning CD8+ T lymphocytes by down-regulation of the activating receptor NKG2D: role of NKG2D ligands released by activated T cells / Cerboni, Cristina; Ardolino, Michele; Santoni, Angela; Zingoni, Alessandra. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 113:(2009), pp. 2955-2964. [10.1182/blood-2008-06-165944]

Detuning CD8+ T lymphocytes by down-regulation of the activating receptor NKG2D: role of NKG2D ligands released by activated T cells.

CERBONI, CRISTINA;ARDOLINO, MICHELE;SANTONI, Angela;ZINGONI, Alessandra
2009

Abstract

NKG2D is an activating receptor expressed on CD8(+)alpha beta(+) T cells, alpha beta(+) T cells, natural killer (NK) cells, and some CD4(+) T cells. For a long time, the interaction of NKG2D with its ligands (NKG2DLs) MICA, MICB, and ULBP1-3 has been considered a mechanism for recognition and elimination of tumor, infected, or otherwise "stressed" cells. However, a new role for NKG2D as an immunoregulatory receptor is emerging. Here, we show that NKG2D is strongly down-modulated on antigen-activated CD8(+) T cells but only if CD4(+) T cells are present. Down-modulation was caused by soluble factors produced by CD4(+) T cells, and in particular soluble NKG2DLs were found in the supernatants of antigen-activated T-cell cultures. MICB was the ligand released at higher levels when CD4(+) T cells were present in the cell cultures, suggesting that it could be the major player of NKG2D down-modulation. CD8(+) T cells expressing low levels of NKG2D had impaired effector functions, as evaluated by proliferation, cytokine production, and cytotoxicity assays after combined triggering of NKG2D and TCR-CD3 complex. These findings show that activated CD4(+) T cells expressing NKG2DLs can efficiently prevent NKG2D-mediated CD8(+) T-cell functions, and suggest that the NKG2D/NKG2DL interaction can regulate immune responses. (Blood. 2009; 113: 2955-2964)
2009
01 Pubblicazione su rivista::01a Articolo in rivista
Detuning CD8+ T lymphocytes by down-regulation of the activating receptor NKG2D: role of NKG2D ligands released by activated T cells / Cerboni, Cristina; Ardolino, Michele; Santoni, Angela; Zingoni, Alessandra. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 113:(2009), pp. 2955-2964. [10.1182/blood-2008-06-165944]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/360097
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