Induction of Plasma (TRAIL), TNFR-2, Fas Ligand and Plasma Microparticles After HIV-1 Transmission: Implications for HIV-1 Vaccine Design.
Death of CD4+, CCR5+ T cells is a hallmark of human immunodeficiency virus infection. We studied the plasma levels of cell death mediators and products - tumor necrosis factor-related apoptosis inducing ligand (TRAIL), Fas ligand, tumor necrosis factor receptor type 2 (TNFR2) and plasma microparticles during the earliest stages of infection following HIV-1 transmission in plasma samples from US plasma donors. Significant plasma TRAIL elevations occurred a mean of 7.2 days before the peak of plasma viral load (VL), while TNFR2, Fas ligand and microparticle elevations occurred coincident with maximum VL. Microparticles have been previously shown to mediate immunosuppressive effects on T cells and macrophages. We found that T cell apoptotic microparticles also potently suppressed in vitro IgG and IgA antibody production by memory B cells. Thus, release of TRAIL during the eclipse phase of HIV-1 transmission may initiate or amplify early HIV-1 induced cell death. The window of opportunity for a HIV-1 vaccine is from HIV-1 transmission until establishment of the latently infected CD4+ T cells. Release of products of cell death and subsequent immunosuppression following HIV-1 transmission could potentially narrow the window of opportunity in which a vaccine has to plausibly extinguish HIV-1, and place severe constraints on the time the immune system has to respond to the transmitted virus.
Gasper Smith, N; Crossman, DM; Whitesides, JF; Mensali, N; Ottinger, JS; Plonk, SG; Moody, MA; Ferrari, G; Weinhold, KJ; Miller, SE; Reich, CF; Qin, L; Self, SG; Shaw, GM; Denny, TN; Jones, LE; Pisetsky, DS; Haynes, BF
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