Evidence for interleukin-1 beta being a necessary but not sufficient co-stimulatory signal in monocyte-dependent anti-CD3-mediated T-cell triggering.
T-cell activation by CD3-specific antibodies is either monocyte independent or monocyte mediated, depending on the fine specificity and mode of presentation of anti-CD3. Monocyte-independent activation occurs when T cells encounter surface-bound antibody at high density, thereby mediating interleukin-2 (IL-2) production. Monocyte-dependent activation occurs upon bipolar binding of anti-CD3 to CD3 of T cells and to Fc receptors of accessory cells (monocytes). We addressed the role of interleukin-1 (IL-1) as a co-stimulatory signal in monocyte-dependent anti-CD3-mediated T-cell proliferation by using specific and anti-IL-1 subtype antibodies and IL-1 receptor antagonist (IL-1ra). IL-1ra blocked proliferation of mononuclear cells (MNC) induced by fluid-phase anti-CD3, and proliferation of nylon wool-purified cells (NWPC; < 1% monocytes) exposed to low-density, but not high-density, anti-CD3 coats. Stimulation of MNC by fluid-phase anti-CD3 and of NWPC by low-density anti-CD3 coats could both be blocked by anti-IL-1 beta, but not by anti-IL-1 alpha, although the latter efficiently blocked IL-1 alpha-mediated thymocyte co-stimulation. Neither the addition of IL-1 beta (given alone or combined with IL-6 and/or IL-1 alpha) nor anti-CD3-independent, LPS-induced cytokine induction in monocytes provided the co-stimulatory signal(s) for anti-CD3-triggered T cells in the absence of bipolar anti-CD3 binding.(ABSTRACT TRUNCATED AT 250 WORDS)
Leutwyler
C
C
Institute of Veterinary Virology, University of Berne, Switzerland.
Schalch
L
L
Jungi
T W
TW
D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D016853:Muromonab-CD3 / Q000494:pharmacology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000276:immunology*
D007375:Interleukin-1; D015850:Interleukin-6; D016853:Muromonab-CD3; D017472:Receptors, Interleukin-1