The small heat shock protein 27 is a key regulator of CD8+ CD57+ lymphocyte survival.
Differences in CD8(+)CD57(-) and CD8(+)CD57(+) lymphocyte lifespan have been documented. Lower numbers and shorter lifespan are characteristic of CD8(+)CD57(+) in normal individuals. However, CD8(+)CD57(+) are expanded in certain disease states including T cell large granular leukemia and other hematologic malignancies. The mechanisms responsible for the differences in CD8(+)CD57(-) and CD8(+)CD57(+) lifespan remain elusive. In this study, we demonstrate that the small heat shock protein (Hsp) 27 is a key regulator of CD8(+)CD57(+) lymphocyte lifespan. We found that Hsp27 expression is significantly lower in CD8(+)CD57(+) than in CD8(+)CD57(-) lymphocytes. In contrast, Hsp60 and Hsp70 are expressed at comparable levels. Unlike other antiapoptotic Bcl-2-like molecules, the expression of Hsp27 tightly correlates with CD8(+)CD57(+) and CD8(+)CD57(-) lifespan. We demonstrate that Hsp27 overexpression in CD8(+)CD57(+) lymphocytes to levels found normally in CD8(+)CD57(-) lymphocytes decreased apoptosis. Accordingly, silencing of Hsp27 in CD8(+)CD57(-) lymphocytes increased apoptosis. Collectively these results demonstrate that Hsp27 is a critical regulator of normal CD8(+)CD57(+) lifespan supporting its use as a marker of lifespan in this lineage, and suggest a mechanism responsible for the decreased apoptosis and clonal expansion characteristic of certain disease states.
Wood
Karen L
KL
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Internal Medicine, Ohio State University, Columbus, OH 43210, USA.
Voss
Oliver H
OH
Huang
Qin
Q
Parihar
Arti
A
Mehta
Neeraj
N
Batra
Sanjay
S
Doseff
Andrea I
AI
D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018959:CD57 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D005819:Genetic Markers / Q000235:genetics; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D018959:CD57 Antigens; D005819:Genetic Markers; D055551:HSP27 Heat-Shock Proteins
Clin Exp Immunol. 1993 Nov;94(2):297-305
7693383
Ann N Y Acad Sci. 2000;926:126-31
11193028
Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):367-74
12663328
Eur J Immunol. 2006 Jul;36(7):1654-8
16791883
Blood. 2006 Jun 15;107(12):4834-40
16484592
Clin Immunol. 2005 Dec;117(3):294-301
16290071
J Immunol. 1995 Jun 1;154(11):6182-90
7538544
Front Biosci (Landmark Ed). 2009 Jan 01;14(7):2413-31
19273209
Mol Cell Biol. 2000 Oct;20(20):7602-12
11003656
Blood Rev. 1999 Dec;13(4):230-40
10741898
Clin Cancer Res. 2008 Dec 15;14(24):8279-87
19088045
Science. 2002 Mar 8;295(5561):1852-8
11884745
J Biol Chem. 2007 Aug 24;282(34):25088-99
17597071
Apoptosis. 2003 Jan;8(1):61-70
12510153
Oncogene. 2000 Apr 13;19(16):1975-81
10803458
Nat Cell Biol. 2000 Sep;2(9):645-52
10980706
Br J Haematol. 1998 Mar;100(3):469-77
9504628
Br J Haematol. 2000 Jul;110(1):203-9
10930999
Arthritis Rheum. 1997 Feb;40(2):237-48
9041935
Am J Respir Crit Care Med. 1994 Apr;149(4 Pt 1):972-80
7511468
Immunology. 2001 Jul;103(3):281-90
11454057
Arthritis Rheum. 1993 May;36(5):608-12
7683880
J Cell Mol Med. 2008 Jun;12(3):743-61
18266962
Blood. 2001 Nov 1;98(9):2817-27
11675356
Blood. 1998 Dec 15;92(12):4771-7
9845544
Leukemia. 1998 Oct;12(10):1573-82
9766502
Blood. 1997 Jan 1;89(1):256-60
8978299
Breast Cancer Res Treat. 1999 Jul;56(2):187-96
10573111
Hematol J. 2003;4(1):18-25
12692516
Blood. 2003 Apr 1;101(7):2711-20
12433688
J Biol Chem. 1996 Jul 12;271(28):16510-4
8663291
J Immunol. 1981 Sep;127(3):1024-9
6790607
J Clin Immunol. 1986 Nov;6(6):502-9
3097061
J Immunol. 1995 Nov 15;155(10):5046-56
7594513
J Clin Invest. 2001 Feb;107(3):351-62
11160159
Clin Exp Immunol. 2005 Feb;139(2):268-78
15654825
Front Biosci (Landmark Ed). 2009 Jan 01;14(10):3771-81
19273309
Am J Hematol. 2007 Dec;82(12):1103-5
17626255
Blood. 1991 May 15;77(10):2237-41
1709378