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