Production of granulocyte-macrophage colony-stimulating factor by large
granular lymphocytes stimulated with Candida albicans: role in activation
of human neutrophil function
DK Blanchard, MB Michelini-Norris and JY Djeu
Department of Medical Microbiology and Immunology, University of South
Florida College of Medicine, Tampa 33612.
In the present study, culture supernatants from larger granular lymphocytes
(LGL) that were activated with Candida albicans antigens were shown to
stimulate the ability of neutrophils to inhibit fungal growth.
Identification of the activation factors showed that granulocyte-macrophage
colony-stimulating factor (GM-CSF), a hematopoietic growth factor, was
involved. Human peripheral blood mononuclear cells were fractionated by
Percoll density centrifugation and each subpopulation of cells was
stimulated with C albicans yeast cells. GM-CSF was produced in those
fractions enriched for LGL, but not T lymphocytes or adherent monocytes.
Additionally, the phenotype of the GM-CSF-producing cell was found to be
CD2+, CD16+, HLA-DR+, and negative for CD4, CD8, and CD15. Kinetic studies
demonstrated that GM- CSF appeared in the supernatants within 2 days of
culture and continued to be produced up to 7 days. Optimal stimulation of
LGL was seen at a ratio of 3 heat-killed C albicans yeast cells per LGL.
Thus, LGL play an important role in host defense against this opportunistic
pathogen by producing cytokines, including GM-CSF, which in turn activates
the fungicidal activity of neutrophils.
Volume 77,
Issue 10,
pp. 2259-2265,
05/15/1991
Copyright © 1991 by The American Society of Hematology