Parasite antigen-driven basophils are a major source of IL-4 in human filarial infections.
Basophil contribution to the IL-4 pool in filarial infections was assessed using PBMC from 20 patients with active filarial infections and from 9 uninfected subjects. Patient basophils released histamine in response to Brugia malayi Ag (BmAg). They also released IL-4 within 2 h after exposure to BmAg, as assessed by intracellular cytokine flow cytometry. This IL-4 induction was Ag specific, as IL-4 was not detected in BmAg-exposed basophils obtained from uninfected subjects. Although there were, on average, 64 times more CD4(+) T cells than basophils in the peripheral circulation of filaria-infected patients, the absolute numbers of basophils and CD4(+) T cells producing IL-4 per 100000 PBMC were equivalent (geometric mean: 16 IL-4-producing basophils/100000 PBMC vs 22 IL-4-producing CD4(+) T cells/100000 PBMC). Basophils also released IL-4 in response to both low and high concentrations of BmAg, whereas CD4(+) T cells released IL-4 only after incubation with a high concentration of BmAg, raising the possibility that basophils, due to their lower threshold for activation, may actually release IL-4 more frequently than CD4(+) T cells in vivo. Furthermore, IL-4 production in vitro by Ag-stimulated purified basophils or CD4(+) T cells provided evidence that basophils release greater quantities of IL-4 per cell than CD4(+) T cells in response to BmAg. These results suggest that, when Ag-specific IgE is present in a filaria-infected individual, basophils function to amplify the ongoing Th2 response by releasing IL-4 in greater amounts and possibly more frequently than CD4(+) T cells in response to filarial Ag.
Mitre
Edward
E
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. emitre@niaid.nih.gov
Taylor
Rebekah T
RT
Kubofcik
Joseph
J
Nutman
Thomas B
TB
D000818:Animals; D000947:Antigens, Helminth / Q000502:physiology*; D001491:Basophils / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D017178:Brugia malayi / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D002452:Cell Count; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005368:Filariasis / Q000276:immunology* / Q000469:parasitology*; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male
D000947:Antigens, Helminth; D018793:Interleukin-13; D015847:Interleukin-4