Down-regulation of cytokine production and interleukin-2 receptor expression by pooled human IgG.
The influence of pooled human IgG preparations for intravenous use (i.v.Ig) on in vitro-induced cytokine production was studied at the single-cell level using cytokine-specific monoclonal antibodies (mAb) and indirect immunofluorescent technique. Cultured mononuclear cells from peripheral blood from healthy adult donors were polyclonally stimulated for 96 hr by either direct ligation of T-cell receptors using immobilized anti-CD3 mAb or by a combination of a protein kinase C activator [phorbol 12-myristate 13-acetate (PMA)] and a calcium ionophore (ionomycin) in the absence or presence of i.v.Ig. A marked inhibition of proliferation and blast transformation was noted in all i.v.Ig exposed cultures, despite good cell survival. The production of the T-cell lymphokines interleukin-2 (IL-2), IL-10,interferon-gamma (IFN-gamma) and tumour necrosis factor-beta (TNF-beta) was significantly down-regulated during the whole studied period in the i.v.Ig containing anti-CD3 stimulated cultures. The synthesis of the monokine IL-8 was not suppressed and that of TNF-alpha, which was made by both lymphocytes and monocytes, was only moderately inhibited. Somewhat different and more transient effects were observed in the i.v.Ig-exposed PMA/ionomycin-activated cultures. The production of IL-2, IL-3, IL-4, IL-5, IL-10, TNF-beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) was down-regulated during the initial phase of the cultures up to 48 hr, but not at 48-96 hr. The synthesis of IFN-gamma and TNF-alpha was unaffected of the influence of i.v.Ig during the entire culture period. The expression of IL-2 receptors (IL-2R) was significantly suppressed in the i.v.Ig-treated anti-CD3-activated cells, but not in the PMA/ionomycin-stimulated cultures. Taken together our results indicate that pooled IgG may mediate immunomodulation by direct effects on cytokine production and on T-cell proliferation.
Andersson
U G
UG
Department of Immunology, Arrheniuslaboratories for Natural Sciences, Stockholm University, Sweden.
Björk
L
L
Skansén-Saphir
U
U
Andersson
J P
JP
D000954:Antigens, Surface / Q000032:analysis; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D015759:Ionomycin / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000954:Antigens, Surface; D017252:CD3 Complex; D016207:Cytokines; D007074:Immunoglobulin G; D016898:Interferon-alpha; D007378:Interleukins; D008233:Lymphotoxin-alpha; D015375:Receptors, Interleukin-2; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate