Characterization of thymic cell subpopulations involved in IL-1- or GM-CSF-induced IL-6 production.
IL-6 has been demonstrated by in vitro studies to be a cytokine involved in thymocyte activation We show herein that thymocytes cultured at high concentrations in the absence of comitogen respond to IL-1 and, to a lesser degree, to GM-CSF, by producing IL-6. This phenomenon disappears rapidly with decreasing cell densities, suggesting the involvement of a minor cellular component of the thymus which may be solely responsible for or cooperate in IL-6 production. We have analysed several thymic subpopulations for IL-6 production and show that accessory cells, and eventually their precursors, are the major if not exclusive, producers of this cytokine. Mature steroid-resistant thymocytes do not secrete IL-6. Production of IL-6 by total CD4-CD8- thymic cells is largely reduced by the depletion of mature accessory cells which express I-A and Mac-1 antigens. As shown previously, accessory cell precursors within the CD4-CD8- compartment are induced to differentiate into M phi and DC in response to IL-1 and GM-CSF. We provide evidence that this maturation is associated with IL-6 production. Thymic DC and phagocytic cells of the thymic reticulum (P-TR) in vitro produce high levels of IL-6 which are enhanced by GM-CSF or IL-1. These factors have a synergistic effect on IL-6 production by total thymocytes, and on CD4-CD8- cells that are not depleted for mature I-A+ Mac-1+ accessory cells.(ABSTRACT TRUNCATED AT 250 WORDS)
U. 345 INSERM, CHU Necker-Enfants Malades, Paris, France.
M
M
Papiernik
A
A
Herbelin
E
E
Schneider
M
M
Dy
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D010586:Phagocytes / Q000378:metabolism; D016176:T-Lymphocyte Subsets; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor