Plasma Cytokine Levels and HIV-Specific

G TURK; N LAUFER; AM RODRIGUEZ; Y GHIGLIONE; J FALIVENE; MJ RUIZ; O SUED; L GIAVEDONI; P CAHN; H SALOMÓN; MM GHERARDI

Boston

Congreso; AIDS Vaccine 2012; 2012

AIDS VACCINE 2012

􀀑􀄂􀄐􀅬􀅐􀆌􀅽􀆵􀅶􀄚􀍗􀀃It is believed that ini􀆟al encounter between HIV and the human host triggers a comple􀇆 series of events that dictate future disease course. Inter-individual di􀄫erences among the host-players involved in these processes seem to early determine di􀄫erent rates of disease progression. Here we were aimed at studying the rela􀆟onship between innate and adap􀆟ve soluble immune mediators, HIV-speci􀄮c T-cell response and the course of acute infec􀆟on. 􀁄􀄞􀆚􀅚􀅽􀄚􀆐􀍗􀀃 Plasma levels of 37 cytokines were measured by 􀀾umine􀇆 technology in di􀄫erent groups of volunteers􀍗 10 healthy donors 􀍾HD􀍿 and 50 HIV infected-sub􀅩ects􀍗 10 chronics, 12 aviremic controllers 􀍾􀀜C􀍿 and 28 sub􀅩ects enrolled during acute infec􀆟on 􀍾AI􀍿. All HIV pa􀆟ents were o􀄫-HAART. Fro􀇌en P􀀑MCs from the same individuals were used to determine HIV-speci􀄮c T-cell responses by IFN-gamma ELISPOT. Data was compared inter- and intra-groups and correlated to viral load 􀍾VL􀍿, CD4 T cell counts and both virological 􀍾VL􀍿 and immunological 􀍾CD4 count􀍿 set-points 􀍾in AI􀍿, using parametric and non-parametric sta􀆟s􀆟cs. R􀄞􀆐􀆵􀅯􀆚􀆐􀍗􀀃Compared to HD, cytokines signi􀄮cantly elevated during acute and chronic infec􀆟on included IL-1alfa, IL-10, IP-10 and TNF-alfa. Conversely, IL-12p40 and the macrophage-derived chemokine 􀍾MDC􀍿 were only signi􀄮cantly elevated in chronics and not in AI subjects who showed similar levels to HD and even EC. Moreover, levels of IL-12p40, IL-12p70 and MDC directly correlated with CD4 T-cell count among chronics and both CD4 T-cell count and immunological set point in AI. Regarding HIVspeci 􀄮c T-cell response during AI, propor􀆟on of 􀀧ag-speci􀄮c and Nef-speci􀄮c cells signi􀄮cantly correlated 􀍾directly and inversely, respec􀆟vely􀍿 with immunological set point 􀀒􀅽􀅶􀄐􀅯􀆵􀆐􀅝􀅽􀅶􀍗􀀃 Both early and late components of the immune system help preserve CD4 T-cell subset in HIV􀐽 subjects􀍗 key cytokines involved in the ini􀆟a􀆟on and regula􀆟on of cellular immune response and an􀆟-􀀧ag speci􀄮city of e􀄫ector T-cells. These features should be taken into account during vaccine formula􀆟on design to boost favorable results.