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.