Evidence that interleukin-4 suppression of lymphokine-activated killer cell induction is mediated through monocytes.
Recombinant human interleukin-4 (IL-4) and transforming growth factor-beta (TGF-beta) reduce recombinant interleukin-2 (IL-2) induction of lymphokine-activated killer (LAK) cell activity from human peripheral blood mononuclear cells (PBMC). Monocytes can be removed from PBMC by adherence, leaving a peripheral blood lymphocyte population (PBL) which also responds to IL-2 to generate LAK activity. PBL generation of LAK cytotoxicity is susceptible to inhibition by TGF-beta, but not by IL-4. Readdition of purified monocytes to PBL is accompanied by return of the suppressive action of IL-4 on the generation of LAK activity. Induction of LAK cytolysis from Percoll-isolated T cells (greater than 90% CD3+) is also refractory to the inhibitory effect of IL-4. When PBMC were cultured in IL-2, with and without IL-4, subsequent sorting of CD3+ and CD3- lymphocytes by flow cytometry demonstrated that IL-4 had suppressed LAK induction in both effector populations. This suggests that, although isolated CD3+ cells are not susceptible to IL-4 suppression of IL-2 activation, they are sensitive to inhibition when part of a mixed PBMC population. Evidence is presented for the first time that this suppression is mediated via the action of IL-4 on monocytes.
Brooks
B
B
Department of Experimental and Clinical Microbiology, University of Sheffield Medical School, U.K.
Parry
H
H
Lawry
J
J
Rees
R
R
D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
D016212:Transforming Growth Factor beta; D015847:Interleukin-4