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Pathogens can find their ways to most sites in the host. Pathogen sensors, such as Toll-like receptors (TLRs), must be equally and broadly distributed on immune cells to combat them through innate and adaptive immunity. Most classes of TLRs are found in innate immune cells to obtain an immediate response against pathogens, but recent studies indicate that a number of TLRs are wildly expressed in T and B cells, suggesting TLRs also directly regulate adaptive immune responses. Due to the rapid increase of new information on the multiple roles of TLRs, in this paper we aim to review several main properties of TLRs and their direct role in T and B cells. This review consists of 6 parts: (i) Characteristics of Toll-like receptors (TLRs) and signaling; (ii) signalling pathways of TLRs; (iii) TLR expressions on human leukocytes; (iv) TLR expressions and functions in the Thi, CD4+CD45RO+ memory T cells and regulatory/suppressor T as well as B cell populations; (v) therapeutic potential of TLR agonists; (Vi) discussion and perspective. The latest findings and potential therapeutic applications are discussed. There is growing evidence supporting the concept that TLR activation contributes not only to innate immunity but also to adaptive immunity, including direct regulation of both T and B lymphocytes by TLRs. [ABSTRACT FROM AUTHOR]