MicroRNA-155 (miR-155) is upregulated in primary effector CD8 T cells but is expressed at low amounts in naïve cells. Anti-viral CD8 T cell responses and viral clearance were impaired in miR-155 deficient (bic-/-) mice, and this defect was intrinsic to CD8 T cells, as adoptively transferred bic-/- CD8 T cells generated greatly reduced primary and memory responses during infection. To understand the mechanism by which miR-155 regulates CD8 T cell activation, we analyzed the gene expression profiles of naive and in vitro activated wild-type and bic-/- CD8 T cells. CD8 T cells were purified from uninfected C57BL/6 mice and stimulated in vitro with plate-bound anti-CD3 and anti-CD28 antibodies for 48 h or left unstimulated. RNA from these CD8 T cells was processed, amplified, labeled, and hybridized to Affymetrix GeneChip MoGene 1.0 st microarrays.