Human NK cells display major phenotypic and functional changes over the life span

Aging Cell - Tập 9 Số 4 - Trang 527-535 - 2010
Magali Le Garff‐Tavernier1,2,3, Vivien Béziat2,3, Julie Decocq2,4,3, Virginie Siguret5,6, Frédérique Gandjbakhch7,3, Stéphane Lehéricy8, Patrice Debré2,3, Hélène Merle‐Béral1,9,3, Vincent Vieillard2,3
1AP-HP, Hôpital Pitié-Salpêtrière, Service d’Hématologie Biologique, F-75013, Paris, France
2INSERM, UMR-S 945, F-75013, Paris, France
3UPMC Université Paris 06, F-75005 Paris, France
4Laboratoire français de fractionnement et des biotechnologies (LFB), F-91940, Les Ulis, France
5AP-HP, Hôpital Charles-Foix, Laboratoire d’Hématologie, F-94205, Ivry sur Seine, France
6Université Paris Descartes, F-75006 Paris, France
7AP-HP, Hôpital Pitié-Salpêtrière, Service de Rhumatologie, F-75013, Paris, France
8Hôpital Charles-Foix, AP-HP, Service de Gériatrie, F-94205, Ivry sur Seine, France
9Centre des Cordeliers, INSERM UMR-S 872, F-75006, Paris, France

Tóm tắt

SummaryAging is generally associated with an increased predisposition to infectious diseases and cancers, related in part to the development of immune senescence, a process that affects all cell compartments of the immune system. Although many studies have investigated the effects of age on natural killer (NK) cells, their conclusions remain controversial because the diverse health status of study subjects resulted in discordant findings. To clarify this situation, we conducted the first extensive phenotypic and functional analysis of NK cells from healthy subjects, comparing NK cells derived from newborn (cord blood), middle‐aged (18–60 years), old (60–80 years), and very old (80–100 years) subjects. We found that NK cells in cord blood displayed specific features associated with immaturity, including poor expression of KIR and LIR‐1/ILT‐2 and high expression of both NKG2A and IFN‐γ. NK cells from older subjects, on the other hand, preserved their major phenotypic and functional characteristics, but with their mature features accentuated. These include a profound decline of the CD56bright subset, a specific increase in LIR‐1/ILT‐2, and a perfect recovering of NK‐cell function following IL2‐activation in very old subjects. We conclude that the preservation of NK cell features until very advanced age may contribute to longevity and successful aging.

Từ khóa


Tài liệu tham khảo

10.1016/j.jim.2004.08.008

10.1111/j.1365-2567.2007.02555.x

10.1038/leu.2008.343

10.1016/S0531-5565(98)00076-X

10.1016/j.it.2005.02.007

10.1038/35869

10.1016/S0531-5565(01)00162-0

10.1111/j.1600-065X.2006.00457.x

10.1182/blood-2007-09-077438

10.4049/jimmunol.179.1.89

10.1186/1742-4933-3-10

10.4049/jimmunol.173.10.6418

10.1007/s10522-006-9062-6

10.1111/j.1600-065X.2006.00451.x

10.1111/j.1399-0039.2007.00891.x

10.1016/j.coi.2004.01.009

10.1016/j.bbrc.2004.01.027

10.1146/annurev.immunol.23.021704.115526

10.1084/jem.20052554

10.1016/j.mad.2005.01.004

Mariani E, 1998, Age‐dependent decreases of NK cell phosphoinositide turnover during spontaneous but not Fc‐mediated cytolytic activity, Int. Immunol., 10, 981, 10.1093/intimm/10.7.981

10.1046/j.1365-2249.1999.00855.x

10.1126/science.273.5271.70

10.1111/j.0105-2896.2005.00263.x

10.1111/j.1474-9728.2004.00107.x

10.1016/S0047-6374(03)00023-X

10.1016/j.coi.2004.07.010

10.1111/j.1600-065X.2006.00450.x

10.1182/blood-2004-10-4113

10.1038/sj.leu.2405041

10.1006/clin.1997.4401

Pawelec G, 2008, Immunity and ageing in man: Annual Review 2006/2007, Exp. Gerontol., 43, 34

10.1189/jlb.1103592

10.1111/j.1365-2567.2008.03027.x

Ravaglia G, 2000, Effect of micronutrient status on natural killer cell immune function in healthy free‐living subjects aged >=90 y, Am. J. Clin. Nutr., 71, 590, 10.1093/ajcn/71.2.590

10.1017/S0959259898008028

10.1056/NEJM200006223422501

10.4049/jimmunol.178.8.4947

10.1038/nature04606

10.1016/S0531-5565(99)00008-X

10.1016/j.immuni.2006.05.003

10.1111/j.1365-3083.2007.01980.x

10.1203/01.PDR.0000069704.25043.BA

Tilden AB, 1986, Subpopulation analysis of human granular lymphocytes: associations with age, gender and cytotoxic activity, Nat. Immun. Cell Growth Regul., 5, 90

10.1002/eji.200425100

10.1038/nri1306

10.1038/ni1582

10.4049/jimmunol.178.6.3536

10.4049/jimmunol.166.6.3933

10.1182/blood-2009-04-215491

Thông tin
Thông tin xuất bản

Aging Cell

Tập 9 Số 4

527-535

Thông tin tác giả