Co-stimulation-induced release of pro-inflammatory cytokine interleukin-8 by allergen-specific T cells.
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 in vitro mitogenic or co-mitogenic stimulation, cypress-specific T-cell clones (TCC) were generated from five allergic subjects during in vitro seasonal exposure to the allergen. Purified cypress extract was produced directly from freshly collected pollen and used for in vitro 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 in vitro 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.
Spinozzi
F
F
Department of Medicine, University of Perugia, Italy.
Agea
E
E
Piattoni
S
S
Bistoni
O
O
Grignani
F
F
Bertotto
A
A
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D011058:Pollen / Q000276:immunology*; D018418:Th2 Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism*
D000485:Allergens; D000939:Epitopes; D016209:Interleukin-8