Cascades of transcriptional induction during human lymphocyte activation

Lymphocyte activation is known to be associated with the induction of genes implicated in cytokine signaling and cellular proliferation. High-density microarrays offer the means to monitor global cellular expression profiles, temporal relationships between classes of transcripts, and alterations ass ociated with human disease or immunosuppression, We sought to determine whe ther microarray analysis would accurately reflect the normal pattern of gen e expression following human T cell activation, and whether the complex exp ression patterns identified could be analyzed to produce a functional profi le of lymphocyte activation. We examined a time course of sequential expres sion profiles for 6800 cellular transcripts in human lymphocytes activated with concanavalin A. Expression patterns were grouped using clustering anal ysis and validated using Northern blotting. Genes known to be induced follo wing T cell activation were accurately identified, and the qualitative patt erns of gene expression were well correlated between Northern and microarra y analyses. Quantitative differences in gene expression levels were less we ll correlated between these two techniques, Expression profile analysis rev ealed the sequential induction of groups of functionally similar genes, who se temporal coregulation underscores known cellular events during T cell ac tivation, This functional "fingerprint" of lymphocyte activation may prove useful for comparisons of lymphocyte responses under experimental condition s and in disease states.