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Blood. 2012 Apr 19;119(16):3734-43. doi: 10.1182/blood-2011-11-392951. Epub 2012 Mar 1.

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

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1
Hawaii Center for AIDS, Department of Tropical Medicine, University of Hawaii, John A. Burns School of Medicine, Honolulu, 96813, USA. lndhlovu@hawaii.edu

Abstract

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 CD56(dim)CD16(+) NK cells and is expressed heterogeneously in the immature CD56(bright)CD16(-) NK-cell subset in blood from healthy adults and in cord blood. Tim-3 expression was induced on CD56(bright)CD16(-) 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.

PMID:
22383801
PMCID:
PMC3335380
DOI:
10.1182/blood-2011-11-392951
[Indexed for MEDLINE]
Free PMC Article

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