European Journal of Immunology · 2001 · 53 citations · 19 references
Life SciencesImmunologyInfectious DiseasesCellular ImmunologyClinical ImmunologyImmunotherapyAntiretroviral TherapyCell-mediated ImmunityEffector T Cell FunctionLymphocyte ActivationT Cell ActivationT Cell BiologyCd4 Positive T CellsCd4 T Cell ActivationCd8 Positive T CellsCell Proliferation IndicesCell Proliferation KineticsImmunological MechanismsImmunological ResponseT-cell Immune Responses
To characterize the immunological effects of intermittent IL-2 therapy, which leads to selective increases in CD4+ T lymphocytes in HIV-infected patients, 11 patients underwent extensive immunological evaluation. While IL-2 induced changes in both CD4+ and CD8+ cell number acutely, only CD4+ cells showed sustained increases following discontinuation of IL-2. Transient increases in expression of the activation markers CD38 and HLA-DR were seen on both CD4+ and CD8+ cells, but CD25 (a chain of the IL-2 receptor) increased exclusively on CD4+ cells. This increase in CD25 expression was sustained for months following discontinuation of IL-2, and was seen in naive as well as memory cells. IL-2 induced cell proliferation, but tachyphylaxis to these proliferative effects developed after 1 week despite continued IL-2 administration. It thus appears that sustained CD25 expression selectively on CD4+ cells is a critical component of the immunological response to IL-2, and that intermittent administration of IL-2 is necessary to overcome the tachyphylaxis to IL-2-induced proliferation.
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Richard T. Davey, Niranjan Bhat, Christian Yoder et al. · Proceedings of the National Academy of Sciences · 1999 · 856 citations
Mark Connors, Joseph A. Kovacs, Seth Krevat et al. · Nature Medicine · 1997 · 525 citations