Interleukin-2-induced lymphoproliferative responses

Abstract

Interleukin-2 (IL-2) is capable of both stimulating an in vitro lymphoproliferative response and augmenting non-major-histocompatibility-complex-(MHC)-restricted cytotoxicity. However, there are conflicting reports about the phenotypes of responding cells. In the present studies, we determined phenotypes of Ficoll/Hypaque-separated peripheral blood mononuclear cells stimulated with 50, 100 or 1000 U/ml IL-2; analyses were performed after 1, 3 and 5 weeks. With all concentrations, there was a progressive increase in CD3⁺ cells; after 3–5 weeks more than 90% of the cells reacted with this antibody. However, the proportions of CD4⁺ and CD8⁺ cells proved to be a function of the IL-2 concentration. Cultures containing 50 U/ml or 100 U/ml favored the expansion of the CD4⁺ subset. By contrast, in cultures stimulated with 1000 U/ml, CD8⁺ cells predominated. At baseline, CD8⁺ cells comprised 28±2%; after 3 weeks, this value increased to 51±5%. In addition, the proportion of CD56⁺ (Leu19, NKH-1) cells depended on the amount of IL-2. At 50 U/ml, there was no appreciable change in CD56⁺ cells. However, at 1000 U/ml, CD56⁺ cells increased from 17±1% (day 0) to 39±4% (3 weeks). This increase was primarily due to an expansion of the CD3⁺ CD56⁺ subset (non-NMC restricted cytotoxic T cells). By contrast, natural killer (NK) cells, as measured by the CD16 antibody, steadily declined at all IL-2 concentrations.