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PMID: 20385876 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The small heat shock protein 27 is a key regulator of CD8+ CD57+ lymphocyte survival.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 184 ·No. 10 ·2010-05-15 ·Pages 5582-8

Wood KL, Voss OH, Huang Q, Parihar A, Mehta N, Batra S, Doseff AI

Abstract

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.

MeSH Terms
Apoptosis/genetics,immunology CD57 Antigens/biosynthesis,genetics,metabolism CD8-Positive T-Lymphocytes/cytology,immunology,metabolism Cell Differentiation/genetics,immunology Cell Lineage/genetics,immunology Cell Survival/genetics,immunology Cells, Cultured Clone Cells Down-Regulation/genetics,immunology Gene Expression Regulation/immunology Genetic Markers/genetics HSP27 Heat-Shock Proteins/biosynthesis,genetics,physiology Humans T-Lymphocyte Subsets/cytology,immunology,metabolism
Chemicals
CD57 Antigens Genetic Markers HSP27 Heat-Shock Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wood Karen L
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Internal Medicine, Ohio State University, Columbus, OH 43210, USA.
Voss Oliver H
Huang Qin
Parihar Arti
Mehta Neeraj
Batra Sanjay
Doseff Andrea I
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.0902953
Published
2010-05-15
Epub
2010-00-12
Pages
5582-8
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC3253717
Subset
IM
Grants
NHLBI NIH HHS · R01 HL075040-05 · United States
NHLBI NIH HHS · K08 HL080701 · United States
NHLBI NIH HHS · R01 HL075040 · United States
NHLBI NIH HHS · K08 HL080701-05 · United States
NHLBI NIH HHS · R01 HL075040-01 · United States
External Links
PubMed source DOI: 10.4049/jimmunol.0902953 PMC Full Text View journal details
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