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Relative contributions of human types 1 and 2 T-helper cell-derived
eosinophilotrophic cytokines to development of eosinophilia
EA Wierenga, B Backx, M Snoek, L Koenderman and ML Kapsenberg
Laboratory of Cell Biology and Histology, University of Amsterdam, The
Netherlands.
The relative contributions of type 1 and 2 T-helper (Th1 and Th2) cell-
derived interleukin (IL-5), granulocyte-macrophage colony-stimulating
factor (GM-CSF), and IL-3 were studied in the regulation of sequential
events in the development of eosinophilia. Using eosinophils from normal
donors and neutralizing antibodies that selectively block cytokine
activities, we analyzed the effects of these cytokines in supernatants (SN)
of well-characterized allergen-specific Th2 and Th1 T- lymphocyte clones
(TLC) generated from atopic and nonatopic individuals, respectively.
Eosinophil colony formation from CD34+ bone marrow progenitor cells in
semisolid cultures could be induced both by Th1 and Th2 SN, mainly mediated
by the synergistic effects of GM-CSF and IL-3, whereas IL-5 had only a
minor additive effect. High production of mature eosinophils in liquid
cultures of unseparated mononuclear bone marrow cells could only be induced
by Th2 SN, which could be more than 90% blocked by anti-IL-5, but not by
anti-IL-3 or anti-GM-CSF. Chemotaxis of mature peripheral blood eosinophils
could equally well be induced by Th1 and Th2 SN, although the relative
contribution of the individual cytokines was clearly different in the two
sets of SN. Priming of platelet-activating factor (PAF) release by
peripheral blood eosinophils was regulated by additive effects of the three
cytokines and was stronger induced by the Th2 SN than by the Th1 SN. The
present results indicate that IL-5, GM-CSF, and IL-3 control eosinophils
throughout the course of development of eosinophilia, having different
individual contributions in different compartments. The apparent strong and
selective IL-5-dependence of certain yet undefined steps in eosinophil
production in the bone marrow supports the concept of the generally assumed
causal relation between predominant activation of IL-5-producing Th2 cells
in response to allergens and development of eosinophilia in atopic disease.
Volume 82,
Issue 5,
pp. 1471-1479,
09/01/1993
Copyright © 1993 by The American Society of Hematology

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