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- Title
Co-Stimulation-Induced Release of Pro-Inflammatory Cytokine Interleukin-8 by Allergen-Specific T Cells.
- Authors
Spinozzi, F.; Agea, E.; Piattoni, S.; Bistoni, O.; Grignani, F.; Bertotto, A.
- Abstract
Chemokines, which include interleukin (IL)-8, are a family of pro-inflammatory molecules with potent chemoattractant activity on neutrophils, as well as other cell types. IL-8 can be recovered from many inflammatory sites. To test the hypothesis that Th2-type allergen-specific T cells, known to be the main cell type governing the allergic inflammation, are a source of IL-8 and to investigate whether IL-8 release is influenced by the nature of the <em>in vitro</em> mitogenic or co-mitogenic stimulation, cypress-specific T-cell clones (TCC) were generated from five allergic subjects during <em>in vitro</em> seasonal exposure to the allergen. Purified cypress extract was produced directly from freshly collected pollen and used for <em>in vitro</em> stimulation of PBMC bulk cultures. After 5 days priming and a further 7 day period of IL-2-driven cell expansion, monoclonal antibodies to CD3, CD2 and CD28 were adopted for <em>in vitro</em> restimulation of allergen-specific cell lines or, subsequently, secondary established TCC. The induction of apoptosis was detected by propidium iodide (PI) cytofluorimetric assay. Basal and co-stimulation-induced IL-8 production was measured by an ELISA method. Both cypress-specific T-cell lines and TCC secreted appreciable amounts of IL-8. By cross-linking T-cell lines or Th2 CD4+ TCC with CD3, CD2 or CD28 MoAbs, the authors observed a great stimulation-induced IL-8 secretion, preferentially after CD2 or combined CD2/CD28 stimulation. In addition, CD4+ clones released large amounts of IL-8 into culture supernatants after CD2 stimulation while undergoing programmed cell death (30-40% hypodiploid DNA profile of PI-stained cells). In contrast, CD3 crosslinking was unable to determine the release of IL-8 or the induction of apoptosis. Taken together, these results suggest that incomplete TcR engagement by allergen may lead to the secretion of pro-inflammatory cytokines with a contemporary induction of apoptosis in a significant number of target cells. This phenomenon may represent an additional way for local recruitment of neutrophils and basophils.
- Subjects
TH2 cells; ALLERGENS; T cells; INTERLEUKIN-8; MITOGENS
- Publication
Scandinavian Journal of Immunology, 1996, Vol 44, Issue 1, p80
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1046/j.1365-3083.1996.d01-83.x