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

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

Research output: Contribution to journalArticle

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 dimCD16 + NK cells and is expressed heterogeneously in the immature CD56 brig htCD16 - NK-cell subset in blood from healthy adults and in cord blood. Tim-3 expression was induced on CD56 brightCD16 - 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.

Original languageEnglish (US)
Pages (from-to)3734-3743
Number of pages10
JournalBlood
Volume119
Issue number16
DOIs
StatePublished - Apr 19 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Ndhlovu, L. C., Lopez-Vergès, S., Barbour, J. D., Brad Jones, R., Jha, A. R., Long, B. R., Schoeffler, E. C., Fujita, T., Nixon, D. F., & Lanier, L. L. (2012). Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood, 119(16), 3734-3743. https://doi.org/10.1182/blood-2011-11-392951