Memory phenotype of HIV-1 specific CD8 T-cell responses.

YANINA GHIGLIONE; JULIANA FALIVENE; MARÍA JULIA RUIZ; NATALIA LAUFER; MARÍA MAGDALENA GHERARDI; HORACIO SALOMÓN; GABRIELA TURK

Buenos Aires

Jornada; Conferencias Magistrales, Dr FranÇoise Barré-Sinoussi: ?To the HIV cure?; 2013

Instituto INBIRS y el IMBS

INTRODUCTION:Memory CD8+ T-cells are important components of protective immunity. Understanding their development during primary HIV infection (PHI) would contribute to optimal vaccine design. In this work, we analyzed the distribution of total and HIV-specific CD8+ T-cell differentiation phenotypes, during acute/early infection, and their correlation with clinical parameters. MATERIALS & METODOS:Samples: Frozen PBMCs from 44 HIV+ PHI subjects (baseline samples), 11 HIV+ elite controllers (EC), 16 HIV+ Chronics, and 10 healthy donors (HD) were used. For PHI subjects, viral and CD4 set points were calculated as the geometric mean of the viral load and CD4 T-cell count determinations obtained between 6 and 12 months after the presumed date of infection. Antigens: HIV-1 PTE Gag, Env and Nef peptides were used to stimulate cells. CEF peptide pool, PMA/Ionomycin and DMSO were used as controls. Analysis: HIV-specific T-cell responses were evaluated by IFN-γ ELISPOT. Phenotypic (CD45RO and CCR7) and functional markers (cytokines: IFN-g, IL-2 and TNF-a) were used to identify total and HIV-specific CD8+ memory populations by flow cytometry. Also, cellular activation markers (CD38 and HLA-DR) were analized. RESULTS:EC showed a higher proportion of TNAIVE (40.1%) compared to Chronics (21.4%) and PHI subjects (29.6%, p>0.05). In contrast, the proportion of TEM was significantly higher in Chronics (16.4%) compared to EC (8.8%), PHI (4.6%) and HD (6.5%) groups. When PHI subjects were segregated into PHI350, no differences were observed. Among PHI subjects, Spearman´s correlation showed that the proportion of total TNAIVE cells was directly associated with baseline CD4 T-cell count and inversely with CD4 immune activation. Conversely, the percentage of TEM cells inversely correlated with baseline CD4 T-cell count, immune set point (not shown); and directly with CD8 immune activation. The same significant associations within the specific compartment were observed. Additionally, a direct significant correlation between the HIV-specific TEM cells and viral set point was observed. CONCLUSION:EC and PHI