Leukotriene B4augmentsinterleukin-2 receptor-beta (IL-2Rf) expression andIL-2Rf-mediated cytotoxic response inhuman peripheral bloodlymphocytes

SUMMARY Interleukin-2 caninduce cytolytic activity inhumanperipheral blood lymphocytes andthis activation ismediated bythePchain oftheinterleukin-2 receptor-beta (IL-2Rf3). Leukotriene B4(LTB4) isa potent lipid inflammatory mediator whichinduces IL-2andinterferon-gamma (IFN-y) production fromTcells. Weexamined theability ofLTB4tomodulate IL-2-induced cytolytic activity. Peripheral blood lymphocytes which hadbeenpreincubated for24hrinthepresence ofLTB4responded to100fold lower concentrations ofIL-2withanaugmentation ofnatural killer (NK)cell cytotoxic activity. Furthermore, incubation oflymphocytes withgraded concentrations ofLTB4augmented the proportion ofIL-2Rf+ cells. Peakactivity wasseenat10nmLTB4andwascomparable tothatof PHA.Bytwo-colour cytofluorometry, theincreased expression ofIL-2Rf wasfoundpredominantly onCD56+cells andtoalesser extent onCD8+cells, while CD4+cells wereunaffected. These observations werecorrelated atthemessenger RNA (mRNA)level withincreased IL-2Rf mRNA accumulation following stimulation ofpurified CD56+andCD8+cells withLTB4.CD56-,CD8cells didnotrespond toLTB4byincreased IL-2RJmRNA accumulation. Ourdataindicate, forthe first time, that LTB4canmarkedly increase thesensitivity ofnon-major histocompatibility complex (MHC)-restricted cytotoxic lymphocytes toIL-2, intermsofIL-2-dependent cytotoxic responses, andthatthissensitivity isassociated withaugmented IL-2RBgenemessage andcellsurface expression.