2012
DOI: 10.1182/blood-2011-11-392951
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Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity

Abstract: IntroductionNatural killer (NK) cells comprise 5% to 20% of human peripheral blood lymphoid cells and are a critical component of the immune system, providing protection against viral infections and contributing to tumor immune surveillance. NK-cell activity is regulated by an intricate balance of signals transmitted by inhibitory and activating receptors. 1,2 Functionally distinct NK-cell subsets can be defined based on the level of CD56 and CD16 coexpression. 3 CD56 bright CD16 Ϫ NK cells produce abundant IF… Show more

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Cited by 427 publications
(422 citation statements)
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“…Tim-3 was found to act as a marker of activation or maturation of NK cells and suppress NK cell cytotoxicity. 25 In contrast, other reports have provided evidence that increased Tim-3 expression on NK cells leads to NK cell dysfunction in chronic virus infections, such as hepatitis B and HIV infection. 26,27 Therefore, we propose that the regulatory effects of Tim-3 on NK cells are distinct in different immune microenvironments.…”
Section: Introductionmentioning
confidence: 62%
“…Tim-3 was found to act as a marker of activation or maturation of NK cells and suppress NK cell cytotoxicity. 25 In contrast, other reports have provided evidence that increased Tim-3 expression on NK cells leads to NK cell dysfunction in chronic virus infections, such as hepatitis B and HIV infection. 26,27 Therefore, we propose that the regulatory effects of Tim-3 on NK cells are distinct in different immune microenvironments.…”
Section: Introductionmentioning
confidence: 62%
“…32). Additionally, TIM3 (also known as HAVCR2) 92,93 , which inhibits by a so far undefined mechanism, and the E3 ubiquitin ligase CBL-B, which inactivates the TAM family of receptors (TYRO3, AXL and MER) 94 , have also been shown to inhibit the activation of NK cells. There is emerging evidence that the formation of NK cell memory for HCMV can also occur in individuals carrying a homozygous null allele of KLRC2, which encodes NKG2C 41 .…”
Section: Box 2 | Regulation Of Nk Cells By Activating and Inhibitorymentioning
confidence: 99%
“…However, there are conflicting data surrounding the TIM-3 mediated regulation of innate immunity. In addition to suggesting similar immunosuppressive actions of TIM-3 on innate immune cells, as observed in T cells [14,15], TIM-3 was also found to promote innate immune responses [2,16]. Moreover, several recently published papers report that in reference to viral infections, overexpression of TIM-3 on NK cells was associated with effector dysfunction [17,18].…”
Section: Introductionmentioning
confidence: 95%