RESUMO
OBJECTIVE: To immunophenotype CD4+ and CD8+ T cell sub-populations in HIV-associated immune reconstitution inflammatory syndrome (IRIS). DESIGN: Nested case-control immunological study. METHODS: ART-naïve HIV-infected patients were prospectively observed for IRIS during the first 6 months of ART. Twenty-two IRIS cases and 22 ART-duration matched controls were sampled for T cell immunophenotyping. RESULTS: IRIS cases demonstrated significantly lower CD4 cell counts compared to controls (baseline: 79 versus 142, p = 0.02; enrollment: 183 versus 263, p = 0.05, respectively) with no differences in HIV RNA levels. Within CD4+T cells, cases exhibited more of an effector memory phenotype compared to controls (40.8 versus 27.0%, p = 0.20), while controls trended towards a central memory phenotype (43.8 versus 30.8%, p = 0.07). Within CD8+ T cells, controls exhibited more central memory (13.9 versus 7.81%, p = 0.01, respectively) and effector (13.2 versus 8.8%, p = 0.04, respectively) phenotypes compared to cases, whereas cases demonstrated more terminal effectors than controls (28.8 versus 15.1%, p = 0.05). Cases demonstrated increased activation of CD8+ T cell effector memory, terminal effector, and effector subsets than controls (p = 0.04, 0.02, and 0.02, respectively). CONCLUSION: CD4+ and CD8+ T cell subset maturational phenotypes were heterogeneous among IRIS cases and controls. However, IRIS cases demonstrated significant increases in activation of CD8+ T cell effector subpopulations.
RESUMO
The death of CD4(+) CCR5(+) T cells is a hallmark of human immunodeficiency virus (HIV) infection. We studied the plasma levels of cell death mediators and products--tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), Fas ligand, TNF receptor type 2 (TNFR-2), and plasma microparticles--during the earliest stages of infection following HIV type 1 (HIV-1) transmission in plasma samples from U.S. plasma donors. Significant plasma TRAIL level elevations occurred a mean of 7.2 days before the peak of plasma viral load (VL), while TNFR-2, Fas ligand, and microparticle level elevations occurred concurrently with maximum VL. Microparticles had been previously shown to mediate immunosuppressive effects on T cells and macrophages. We found that T-cell apoptotic microparticles also potently suppressed in vitro immunoglobulin G (IgG) and IgA antibody production by memory B cells. Thus, release of TRAIL during the onset of plasma viremia (i.e., the eclipse phase) in HIV-1 transmission may initiate or amplify early HIV-1-induced cell death. The window of opportunity for a HIV-1 vaccine is from the time of 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 during which a vaccine is able to extinguish HIV-1 infection and could place severe constraints on the amount of time available for the immune system to respond to the transmitted virus.
