Details

Autor(en) / Beteiligte

• Ndhlovu, Lishomwa C.
• Lopez-Vergès, Sandra
• Barbour, Jason D.
• Jones, R. Brad
• Jha, Aashish R.
• Long, Brian R.
• Schoeffler, Eric C.
• Fujita, Tsuyoshi
• Nixon, Douglas F.
• Lanier, Lewis L.

Titel

Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity

Ist Teil von

• Blood, 2012-04, Vol.119 (16), p.3734-3743

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Natural killer (NK) cells are innate lymphocytes that play an important role against viral infections and cancer. This effect is achieved through a complex mosaic of inhibitory and activating receptors expressed by NK cells that ultimately determine the magnitude of the NK-cell response. The T-cell immunoglobulin– and mucin domain–containing (Tim)–3 receptor was initially identified as a T-helper 1–specific type I membrane protein involved in regulating T-cell responses. Human NK cells transcribe the highest amounts of Tim-3 among lymphocytes. Tim-3 protein is expressed on essentially all mature CD56dimCD16+ NK cells and is expressed heterogeneously in the immature CD56brightCD16– NK-cell subset in blood from healthy adults and in cord blood. Tim-3 expression was induced on CD56brightCD16− NK cells after stimulation with IL-15 or IL-12 and IL-18 in vitro, suggesting that Tim-3 is a maturation marker on NK cells. Whereas Tim-3 has been used to identify dysfunctional T cells, NK cells expressing high amounts of Tim-3 are fully responsive with respect to cytokine production and cytotoxicity. However, when Tim-3 was cross-linked with antibodies it suppressed NK cell–mediated cytotoxicity. These findings suggest that NK-cell responses may be negatively regulated when NK cells encounter target cells expressing cognate ligands of Tim-3.