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Th1 and Th2 T-helper cells exert opposite regulatory effects on
procoagulant activity and tissue factor production by human monocytes
G Del Prete, M De Carli, RM Lammel, MM D'Elios, KC Daniel, B Giusti, R Abbate and S Romagnani
Division of Clinical Immunology and Allergology, Istituto di Clinica Medica
3, Florence, Italy.
The role of T-cell subsets in the induction of tissue factor (TF)
production by human monocytes in vitro was investigated. Mitogen
stimulation enabled both unfractionated T cells and their CD4+ or CD8+
subsets to promote procoagulant activity (PCA). After mitogen or antigen
activation, all seven T-cell clones with Th1 cytokine profile, but none of
seven Th2 clones, induced TF production and PCA. T-cell blasts from four
Th1 activated clones were fixed with paraformaldehyde and added to
monocytes in the presence of medium alone or their supernatants. Addition
of either fixed Th1 cells or their supernatants induced low TF production
(0.2 to 0.6 ng/mL), whereas addition of both resulted in much higher TF
synthesis (1.8 to 3.4 ng/mL). Among Th1-type cytokines, only
interferon-gamma (IFN-gamma) induced minimal TF production (0.1 to 0.4
ng/mL). No TF synthesis was induced by activated and fixed Th2 cells and/or
their supernatants, whereas combined addition of fixed Th2 cells and Th1
supernatants or IFN-gamma induced noticeable TF production. The addition of
either anti-IFN-gamma antibody or Th2 supernatants to monocytes stimulated
with activated and fixed Th1 cells plus their supernatant resulted in a
dose-dependent inhibition of TF synthesis, which was partially restored by
neutralization of interleukin-4 (IL-4) or IL-10. Addition of recombinant
IL-4, IL-13, or IL-10, but not IL-5, inhibited the Th1- induced TF
production by monocytes. Data indicate that both CD8+ and CD4+ Th1, but not
Th2, T cells can help TF production and PCA. Both cell-to-cell contact with
activated T cells and Th1-type cytokines, in particular IFN-gamma, are
required for optimal TF synthesis, whereas Th2-derived cytokines (IL-4,
IL-13, and IL-10) are inhibitory. This may be of potential interest for
future therapeutic strategies.
Volume 86,
Issue 1,
pp. 250-257,
07/01/1995
Copyright © 1995 by The American Society of Hematology
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