title: The small heat shock protein 27 is a key regulator of CD8+ CD57+ lymphocyte survival.
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.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Internal Medicine, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wood
authors.forename: Oliver H
authors.initials: OH
authors.lastname: Voss
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.forename: Arti
authors.initials: A
authors.lastname: Parihar
authors.forename: Neeraj
authors.initials: N
authors.lastname: Mehta
authors.forename: Sanjay
authors.initials: S
authors.lastname: Batra
authors.forename: Andrea I
authors.initials: AI
authors.lastname: Doseff
mesh_terms: 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
chemical_list: D018959:CD57 Antigens; D005819:Genetic Markers; D055551:HSP27 Heat-Shock Proteins
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