Human tolerogenic dendritic cells inhibit NK cell-mediated IFN-gamma secretion through soluble factors and cell surface molecules.

DAMIÁN E. AVILA; MARIA V. GIRART; LUCAS E. ROSSI; CAROLINA I. DOMAICA; RAUL G. SPALLANZANI; GABRIEL A. RABINOVICH; NORBERTO W. ZWIRNER

Viña del Mar, Chile

Congreso; 9th Latin American Congress of Immunology; 2009

XII Chilean Society of Immunology Congress. LVII Argentinean Society of Immunology Satellite Scientific Meeting

NK cells establish a crosstalk with immature dendritic cells (iDCs) and mature DCs (mDCs) that involves cell surface receptors such as NKp30 and cytokines such as IL-12, IL-15, IL-18 and IFN-gamma, 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 cells remains unknown. Thus, the aim of this work was to assess 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 to generate tDCs (characterized as IL-12low, IL-10high  and phenotypically 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 that NK cells co-cultured with tDCs or tDC-derived conditioned medium (tDC-CM) produced less IFN-gamma (213±72 pg/ml and 139±66 pg/ml, respectively) than NK cells cultured with fully mature DCs (1319±72 pg/ml, p<0.001). No IFN-gamma secretion was triggered by iDCs and dexamethasone alone had a minor direct inhibitory effect on IFN-gamma secretion by NK cells (709±188 pg/ml, p<0.01). Extensively washed tDCs (but not mDCs) also prevented IFN-gamma secretion by NK cells (202±88 pg/ml vs. 1105±502 pg/ml). Therefore, tDCs diminish NK cell IFN-gamma secretion by tDC-derived soluble factors and most likely, cell surface molecules.