抄録
In the treatment of human cancer, the efficacy of the adoptive transfer of lymphokine-activated killer (LAK) cellsc ombinedw ith interleukin2 (IL2) h as beene mphasizedH. owever, administratioonf l arged oseso f IL2m ayc auses ignificanta dversee ffects, s uch as“capillaryl eaks yndrome”. Moreovert, h e administrationo f corticosteroidm ayr educet he toxicityo fI L2. H owevetrh e efficacyo fa doptivei mmunotherapiys abrogatedb y the administrationo f corticosteroidI. n this context, the effect of corticosteroido n LAICa ctivity and the changeo f membranea ntigenp henotypeo n PBMC (peripherabl loodm ononucleacr ells) w as studiedi n vitro by using methylprednisolon (eM -PSL).
LAK cells were induced from PBMC, which had been separated from the peripheral blood of normal donors, and incubated with IL2 for 4 days. LAICa ctivity was measuredi n a 4 h chromiumr elease assay against K-562 cell and Daudi cell.
The suppression of LAK activityb y M-PSLd ependedo n bothc oncentrationa ndw orkingp eriodo f M-PSL. This inhibitionw as recognizede ven at rather lowd ensities, s uch as 0.5n mol/ml M -PSLA. ndt he proliferation of PBMC after IL2 incubation, which was measuredb y incorporationo f [3H] TdwRa, s reduced dosedependentlyb y M-PSLI. n contrast, pretreatmentw ithin2 4 hourso f PBMCw ith M-PSLr esultedi n no effect on LAICa ctivity. F urthermoreM -PSLh ad no effectw hen addedd irectlyt o a 4 h chromiumr eleasea ssay.
The analysiso f membranea ntigenp henotypeo n PBMCw as performedb y the directi mmunofluorescence method using FITC-labeledm onoclonaal ntibodies. T he proportionso f T cells and NK cells, which were justifieda s precursorso f LAICce lls, increaseda fter IL2 incubationb oth with and withoutM -PSLT. herefore no effecto f M-PSLw as confirmedi n those circumstancesT. he ratioo f HLA-DR (+) cellsi ncreaseda fter IL2 incubation without M-PSL, while M-PSL reduced expression of this antigen. In contrast, IL2 receptor (CD25) (+c) e l) s, m arkerso f T cella nd NK cella ctivation, s ignificantlyin creaseda fter IL2i ncubationw ith or without M-PSL.
These results suggestt hat the inhibitorye ffecto f M-PSLo n LAKa ctivationw as causedn ot by preventing a triggeringp rocesso f activationo fp recursorc ells, b ut by a possiblei nhibitiono fp roliferationt, h ougho ther effectso f corticosteroidre main to bee lucidatedA. lso, i t is emphasizedth at cautions houldb e exercisedi n the administration of corticosteroid in adoptive immunotherapy because of the inhibitory effect induced by M-PSL.
