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

• Published in: The Journal of immunology (1950) Vol. 184; no. 10; pp. 5582 - 5588
• Main Authors: Wood, Karen L, Voss, Oliver H, Huang, Qin, Parihar, Arti, Mehta, Neeraj, Batra, Sanjay, Doseff, Andrea I
• Format: Journal Article
• Language: English
• Published: United States 15.05.2010
• Subjects: Apoptosis - genetics; Apoptosis - immunology; CD57 Antigens - biosynthesis; CD57 Antigens - genetics; CD57 Antigens - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Lineage - genetics; Cell Lineage - immunology; Cell Survival - genetics; Cell Survival - immunology; Cells, Cultured; Clone Cells; Down-Regulation - genetics; Down-Regulation - immunology; Gene Expression Regulation - immunology; Genetic Markers - genetics; HSP27 Heat-Shock Proteins - biosynthesis; HSP27 Heat-Shock Proteins - genetics; HSP27 Heat-Shock Proteins - physiology; Humans; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0902953

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.