CD4 T cell expansions are associated with increased apoptosis rates of T lymphocytes during IL-2 cycles in HIV infected patients
I Sereti, B Herpin, JA Metcalf, R Stevens, MW Baseler… - Aids, 2001 - journals.lww.com
I Sereti, B Herpin, JA Metcalf, R Stevens, MW Baseler, CW Hallahan, JA Kovacs, RT Davey…
Aids, 2001•journals.lww.comObjective and design In an attempt to determine the mechanisms underlying the CD4 T cell
expansions in patients receiving intermittent interleukin (IL)-2, a cohort of 10 HIV infected
patients were studied during a 5-day cycle of IL-2 to measure rates of apoptosis, the
expression of activation markers in CD4 and CD8 T cell subsets and the serum levels of
proinflammatory cytokines. All patients were receiving highly active antiretroviral therapy.
Methods Peripheral blood mononuclear cells were tested pre-and at the completion of IL-2 …
expansions in patients receiving intermittent interleukin (IL)-2, a cohort of 10 HIV infected
patients were studied during a 5-day cycle of IL-2 to measure rates of apoptosis, the
expression of activation markers in CD4 and CD8 T cell subsets and the serum levels of
proinflammatory cytokines. All patients were receiving highly active antiretroviral therapy.
Methods Peripheral blood mononuclear cells were tested pre-and at the completion of IL-2 …
Abstract
Objective and design
In an attempt to determine the mechanisms underlying the CD4 T cell expansions in patients receiving intermittent interleukin (IL)-2, a cohort of 10 HIV infected patients were studied during a 5-day cycle of IL-2 to measure rates of apoptosis, the expression of activation markers in CD4 and CD8 T cell subsets and the serum levels of proinflammatory cytokines. All patients were receiving highly active antiretroviral therapy.
Methods
Peripheral blood mononuclear cells were tested pre-and at the completion of IL-2 treatment with annexin V/7-AAD for the measurement of apoptosis. Phenotypic analyses of T lymphocytes were performed in parallel. Serum levels of interferon (IFN) γ, granulocyte–macrophage colony stimulating factor, IL-6 and tumor necrosis factor (TNF) α were tested by enzyme-linked immunosorbent assay.
Results
IL-2 increased the spontaneous apoptosis rates of CD4 and CD8 T lymphocytes (P= 0.003). Expression of HLA-DR, CD38 and CD95 increased on both CD4 and CD8 T lymphocytes whereas CD25 induction was observed exclusively on CD4 T cells. Significant increases of serum IL-6 and TNFα levels were noted in all patients whereas viral loads remained unchanged.
Conclusion
Administration of IL-2 for 5 days in HIV infected patients leads to enhanced apoptosis of both CD4 and CD8 T cells despite an eventual increase of the CD4 T cell count. A profound activation state with induction of activation markers on T cells and high levels of TNFα and IL-6 accompanies the increased apoptosis during the IL-2 cycle. These data suggest that the CD4 expansions seen in the context of intermittent IL-2 therapy are the net result of increases in both cell proliferation and cell death.
Lippincott Williams & Wilkins