Toll is the founder of a group of pattern recognition receptors, which play a critical role in the innate immunity in Drosophila. At least 13 distinct Toll-like receptors (TLRs), recognising pathogen-associated molecular pattern (PAMPs), have now been identified in humans. Most investigations on TLRs have focused on cells of the innate system. We report here that naïve human T cells expressed high levels of cell surface TLR2 after activation by anti-T cell receptor (TCR) antibody and interferon-alpha. Activated cells produced elevated levels of cytokines in response to the TLR2 ligand, bacterial lipopeptide (BLP). Furthermore, CD4(+)CD45RO(+) memory T cells from peripheral blood constitutively expressed TLR2 and produced IFNgamma in response to BLP. BLP also markedly enhanced the proliferation and IFNgamma production by CD45RO(+) T cells in the presence of IL-2 or IL-15. Thus, TLR2 serves as a co-stimulatory receptor for antigen-specific T cell development and participates in the maintenance of T cell memory. This suggests that pathogens, via their PAMPs, may contribute directly to the perpetuation and activation of long term T cell memory in both antigen dependent and independent manner.