DNA microarray analysis of T cell‐type lymphoproliferative disease of granular lymphocytes

Summary. Lymphoproliferative disease of granular lympho‐ cytes (LDGL) is characterized by the clonal proliferationoflarge granular lymphocytes of either T‐ or natural killer cell origin. To better understand the nature of T cell‐type LDGL, we purified the CD4–CD8+ proliferative fractions from LDGL patients (n=4) and the surface marker‐matched T cells isolated from healthy volunteers (n=4), and compared the expression profiles of 3456 genes using DNA microarray. Through this analysis, we identified a total of six genes whose expression was active in the LDGL T cells, but silent in the normal ones. Interestingly, expression of the gene for interleukin (IL) 1β was specific to LDGL T cells, which was further confirmed by the examination of the serum level of IL‐1β protein. Given its important role in inflammatory reactions, the disease‐specific expression of IL‐1β may have a causative relationship with the LDGL‐ associated rheumatoidarthritis. Spectratyping analysis of the T‐cell receptor repertoire also proved the monoclonal or oligoclonal natureof LDGL cells. These data have shown that microarray analysis with a purified T‐cell subset is an efficient approach to investigate the pathological condition of Tcell‐type LDGL.

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