INVESTIGADORES
RODRIGUEZ Ana Maria
congresos y reuniones científicas
Título:
HIV -mediated up-regulation of invariant chain (CD74) contributes to generalized immune activation in vivo
Autor/es:
YANINA GHIGLIONE; ANA MARÍA RODRIGUEZ; CRISTIAN DE CANDIA; MAURICIO CAROBENE; H.SALOMÓN; GABRIELA TURK
Lugar:
Buenos Aires
Reunión:
Congreso; 1 Congreso Fanco Argentino de Inmunologia; 2010
Institución organizadora:
SAI-Francia
Resumen:
HIV-mediated up-regulation of invariant chain (Ii chain) was reported to occur in cells infected in vitro, but no data is available on primary APC cultures obtained from HIV+ subjects. Also, increased plasma levels of MIF protein (for what surface Ii chain might serve as a receptor) have been reported for HIV+ subjects Aim: To analyze i) Ii chain modulation in HIV+ patient´s APCs and its correlation with clinical parameters ii) the impact of MIF-Ii chain interaction on lymphocyte activation M&M: Monocyte-derived macrophages (MDMs) from 40 HIV+ patients were obtained and Ii chain was analyzed in p24+ cells. For in vitro experiments, MDMs from healthy donors were infected with Nef WT and Nef viral variants, and treated with MIF. Supernatants from these cultures were used to treat cultured lymphocytes. Activation markers were analyzed by FACS and cytokine levels by ELISA Results: All patients but one, showed li chain n-fold up-regulation 1 when infected (iMDMs) vs uninfected MDMs were compared (mean 2.47±1.82). Median Ii chain n-fold up-regulation directly correlated with CD38 and CD38 and HLA-DR expression levels on peripheral B and CD4 T cells, respectively (Spearman's r=0.657, p=0.007, r=0.579, p=0.023 and r=0.657, p=0.007). IL-6 and IL-8 levels where higher in supernatant from MIF-treated p24+/NefWT MDMs cultures when compared to p24+/Nef MDMs. Moreover, these supernatants induced higher activation of CD4+ T cells. Pre-treatment of MDMs with anti-Ii chain mAb BU-45, before addition of MIF, abrogated this effect Conclusion: Ii chain is up-regulated in iMDMs obtained from HIV+ patients and its expression correlate with higher activation of CD4 T cells. In vitro experimental data support the hypothesis that an interaction between Ii chain and MIF would contribute to generate a proinflammatory environment in a Nef-dependent manner. In summary, these results sustain the idea that Nef-mediated up-regulation of Ii chain plays a relevant role in HIV immunopathogenesis