Baseline markers of inflammation and coagulation have been shown to be powerful predictors of adverse outcomes in patients with HIV infection. In a study of South African patients with advanced HIV infection baseline levels of C-reactive protein, interleukin-6 and D-dimer were found to be higher than that in comparable US populations and strongly associated with an increased risk of death. IL-15 is a cytokine involved in the regulation of the immune system with particularly striking effects on the proliferation and activation of NK and CD8 T cells. The IL-15 receptor utilizes its own unique alpha chain and the same beta- and gamma-chains as IL-2. To prepare for human trials in patients with HIV infection, recombinant human IL-15 was produced under conditions of good manufacturing practices (GMP). In a study of rhesus macaques randomized to control, IV bolus or continuous infusion IL-15 for 10 days, continuous infusion was associated with a 100-fold expansion of effector memory CD8+ T cells. HIV-induced immune activation is associated with an expansion of a subset of human CD8+ T cells expressing HLA-DR antigens. These cells have often been described as exhausted and dysfunctional. A detailed study of these cells in HIV patients and HIV uninfected controls revealed that these cells have a restricted T cell receptor repertoire, show evidence of having undergone multiple rounds of cell division despite not having recently engaged their T cell receptors and contain an increased fraction of cells actively proliferating in vivo. No qualitative differences were noted in CD8+HLA-DR+T cells between healthy controls and patients with HIV infection. These data indicate that this population of cells is a part of normal immune regulation that is exaggerated, but not dysfunctional, in the setting of HIV infection.

Project Start
Project End
Budget Start
Budget End
Support Year
23
Fiscal Year
2012
Total Cost
$1,498,149
Indirect Cost
City
State
Country
Zip Code
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