DIRECT STIMULATION OF NK CELLS BY TLR LIGANDS

MARÍA VICTORIA GIRART; MERCEDES BEATRIZ FUERTES; CAROLINA INÉS DOMAICA; NORBERTO WALTER ZWIRNER

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología.; 2005

American Association of Immunology y otras sociedades biomédicas de USA

Toll-like receptors (TLRs) trigger and shape innate and adaptative immune responses. However, little is known about their role in the stimulation of NK cells. Since they express TLR3, TLR7 and TLR9, we used specific agonists (polyI:C, loxoribine and CpGs) to stimulate isolated human NK cells unstimulated or stimulated for 24 h or 5 days with IL-12 or IL-15, and investigated the expression of the activating receptor NKG2D and the cytotoxicity against tumor targets that do not express or express high levels of the NKG2D ligand MICA (MICA- and MICA+, respectively). CpG type A, loxoribine and polyI:C but not CpG type B slightly down-regulated NKG2D on resting NK cells without compromising cytotoxicity. This slight down-regulation was not observed with cytokine-stimulated NK cells. IL-15 induced higher cytotoxicity against MICA- and MICA+ cells compared to IL-12 and it rendered MICA- cells sensitive to NK cell-mediated cytotoxicity. Conversely, cytotoxicity by NK cells stimulated for 24 h with IL-12 and polyI:C was only increased against MICA+ target cells. After 5 days, IL-12-stimulated NK cells lysed MICA- and MICA+ cells equally well. Thus, resting NK cells are not directly stimulated by TLR ligands, with the exception of TLR3 but IL-12 and IL-15 trigger NK cell-mediated cytotoxicity in a way that depends on TLR3 engagement that may depend on a better integration of the activation signaling cascades and involve NKG2D.