Cross-linking Fc receptors on monocytes triggers IL-6 production. Role in anti-CD3-induced T cell activation.
IL-6 is a multifunctional cytokine which is produced by a variety of cells. Therefore it was examined whether anti-CD3-induced T cell activation was associated with the induction of functionally relevant IL-6 in human monocyte accessory cells. Significantly increased amounts of IL-6 were detected in supernatants of anti-CD3-treated PBMC. Stimulation of FACS-sorted greater than 98% pure monocyte accessory cells, but not of highly purified T cells with anti-CD3, resulted in an increased IL-6 production. Furthermore, anti-CD3 significantly enhanced IL-6 mRNA expression in monocyte accessory cells. IL-6 production was not limited to anti-CD3, inasmuch as equivalent IL-6 stimulation could be achieved with a mouse IgG2a isotype control antibody. In contrast to solid phase-bound mouse IgG2a, the soluble form of this antibody failed to induce IL-6 secretion indicating a requirement for Fc gamma RI receptor cross-linking. Moreover, this property may be specific for the Fc gamma RI receptor inasmuch as mouse IgG1 antibodies binding to the Fc gamma RII receptor did not significantly enhance IL-6 production. The role of IL-6 being an additional signal in T cell activation was confirmed by the finding that an anti-IL-6 antiserum was able to suppress anti-CD3-induced T cell activation. These data indicate that binding of anti-CD3 to Fc gamma RI may generate an activation signal towards the monocyte accessory cell leading to the production and secretion of monocyte IL-6, which in turn augments T cell activation, and also may be relevant to a variety of antibody-mediated immune responses against viral and bacterial infections.
Krutmann
J
J
Department of Dermatology II, University of Vienna, Austria.
Kirnbauer
R
R
Köck
A
A
Schwarz
T
T
Schöpf
E
E
May
L T
LT
Sehgal
P B
PB
Luger
T A
TA
D000938:Antigen-Presenting Cells / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D015152:Blotting, Northern; D017252:CD3 Complex; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D009000:Monocytes / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011961:Receptors, Fc / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007074:Immunoglobulin G; D007375:Interleukin-1; D015850:Interleukin-6; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc