Mecanisms of down-regulation of MHC class II (MHC-II) by immune complexes (IC) on human monocytes.

BARRIONUEVO, PAULA; BEIGIER-BOMPADRE, MACARENA; FERNÁNDEZ, GABRIELA; GÓMEZ, SONIA; PALERMO, MARINA; ISTURIZ, MARTÍN

La Habana, Cuba.

Congreso; VIº Congreso Latinoamericano de Inmunología.; 2002

Asociación Latinoamericana de Inmunología (ALAI).

The regulation of MHC-II molecules is a crucial event in the inmune response. We have demostrated that ovalbumin (OA)-rabbit IgG anti-OA IC down-regulate the basal and IFN-g-induced expression of MHC-II on human monocytes trough the secretion of proteases. Previous reports have shown that IC inhibit IFN-g-induced expression of FcgRI by preventing tyrosine phosphorylation of the STAT-1 and this mechanism was also proposed for the MHC-II inhibition. In this study we investigated whether MHC-II expression could be affected by the inhibition of STAT-1 phosphorylation, the effect of the complement on IC-induced down-regulation and the specificity of the IC effect. The results demonstrated that IFN-g was able to induce STAT-1 phosphorylation even in the presence of IC. Normal human serum (NHS) but not heat-inactivated serum (ØNHS), was capable of reducing the effect of IC on the basal expression of MHC-II on human monocytes. The expression of MHC-II was evaluated by flow cytometry and the results are expressed as the percentage of median of fluorescence intensity (%MFI) ± SEM of control cells: a)IC:41±9; b)IC+NHS:103±9; c)IC+ØNHS:46±11; n=5; a) and c) vs control p<0,01. IC were capable of down-regulating the basal expression of MHC-I, ICAM-1 and CD14 although CD11b expression was not modified. These results indicate that: 1) the effect of IC on MHC-II is not mediated through the inhibition of STAT-1 phosphorylation, 2) the activation of the complement system, probably by IC solubilization, could be a crucial step on the regulation of IC-dependent effects, 3) the effect of IC is not specific for MHC-II molecules.