The augmentation of lymphokine-activated killer activity following pulsing of human peripheral blood mononuclear cells with recombinant human interleukin-2.
The short-term exposure of peripheral blood mononuclear cells (PBMC) to recombinant human interleukin-2 (rhIL-2) at 37 degrees C leads to the generation of lymphokine-activated killer (LAK) activity similar in magnitude to that obtained by the exposure of PBMC to rhIL-2 continuously for 3-5 days. In order to investigate whether the required signal for LAK induction occurred during the short exposure to rhIL-2 or at a later point in the induction phase, PBMC were exposed to rhIL-2 for 1 h at 4 degrees C and then exposed to a low-pH wash to remove bound IL-2 from its receptor. PBMC treated in such a way showed increased LAK activity and proliferation compared to cells exposed to rhIL-2 alone. Expression of the p55 (alpha) subunit of the IL-2 receptor was also increased. In order to cause the augmentation, a lowering of the pH below 4.0 was necessary, and exposure of PBMC to low pH alone (in the absence of rhIL-2) failed to cause activation. Another relevant feature was a transient increase in the expression of the p75 subunit of the IL-2 receptor (beta chain) immediately following the exposure to low pH and the release of interferon gamma, tumour necrosis factor alpha and IL-6; activation was blocked by the inclusion of neutralising antisera raised against rhIL-2 and interferon gamma, thus demonstrating that the endogenous release of these cytokines is important for activation.
Carter
C R
CR
Department of Experimental and Clinical Microbiology, University of Sheffield Medical School, UK.
Hancock
B W
BW
Rees
R C
RC
D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013268:Stimulation, Chemical; D013997:Time Factors
D016207:Cytokines; D007376:Interleukin-2; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins