Human tolerogenic dendritic cells inhibit NK cells mediated IFN-γ secretion trough soluble factors and cell surface molecules

ÁVILA, DAMIÁN EZEQUIEL; GIRART, MARÍA VICTORIA; ROSSI, LUCAS EZEQUIEL; DOMAICA, CAROLINA INÉS; SPALLANZANI, RAÚL GERMÁN; RABINOVICH, GABRIEL ADRIÁN; ZWIRNER, NORBERTO WALTER

Viña del Mar, Chile

Congreso; IXo Congreso Latinoamericano de Inmunología; 2009

Asociación Latinoamericana de Inmunología

NK cells establish a crosstalk with immature dendritic cells (iDCs) and mature DCs (mDCs) that involvescell surface receptors and cytokines, leading to mDC and NK cell activation. Conversely, tolerogenic DCs(tDCs) play a pivotal role in the control of the adaptive immune response but their effects on NK cellsremains unknown. Thus, here we investigated the outcome of the cross-talk between tDCs and NK cells.Human monocytes-derived DCs were treated with LPS to generate mDCs or LPS+dexamethasone togenerate tDCs (characterized as IL-12low, IL-10high and identical to mDCs in terms of CD1a, CD14, CD86,CD83 and HLA class II expression), and cultured with isolated NK cells for 24 hours. We observed thatNK cells co-cultured with tDCs or tDC-derived conditioned medium (tDC-CM) produced less IFN-γ(213±72 pg/ml and 139±66 pg/ml, respectively) than NK cells cultured with fully mature DCs (1319±72pg/ml, p<0.001). No IFN-γ secretion was triggered by iDCs and dexamethasone alone had a minor directinhibitory effect on IFN-γ secretion by NK cells (709±188 pg/ml, p<0.01). Extensively washed tDCs (butnot mDCs) also prevented IFN-γ secretion by NK cells (202±88 pg/ml vs. 1105±502 pg/ml). Therefore,tDCs diminish NK cell IFN-γ secretion by tDC-derived soluble factors and most likely, cell surfacemolecules.