title: Fc epsilon receptor-positive cells are a major source of antigen-induced interleukin-4 in spleens of mice infected with Schistosoma mansoni.
abstract: When cultured in vitro with either mitogen or parasite antigens, spleen cells from mice infected with Schistosoma mansoni produce significantly higher levels of IL-4 than splenocytes from control animals. Previous studies suggested that this increase in IL-4 production occurs because of a selective expansion of T helper type 2 (Th2) cells in infected mice. However, these experiments employed unfractionated spleen populations rather than purified T lymphocytes. Here we demonstrate that T-depleted spleen cells from infected animals synthesize high levels of interleukin-4 (IL-4), but no IL-5 when stimulated with parasite antigen in vitro. Nevertheless, when purified by sorting, T cells and non-B, non-T (NBNT) populations produced similar amounts of IL-4 in response to parasite antigen. The IL-4 producing NBNT cells were found to belong to an Fc epsilon receptor (Fc epsilon R)-positive population which after sort purification produced high levels of IL-4 (between 1000 and 2000 U of per 5 x 10(3) cells). FACS analysis revealed that these Fc epsilon R+ cells make up 0.53% of splenic NBNT cells in control animals while in 8-9-week-infected animals they increase to 3.8% of that population. In contrast, in mice with 8-week unisexual worm infections these cells comprise only 1.71% of NBNT cells, indicating that eggs are a major stimulus of the response. The expansion of Fc epsilon R+ cells and their production of IL-4 could be an important factor regulating the selection and induction of different CD4+ subsets in schistosome-infected hosts.
authors.affiliation: Immunology and Cell Biology Section, NCI, NIH, Bethesda, MD 20892.
authors.forename: M E
authors.initials: ME
authors.lastname: Williams
authors.forename: M C
authors.initials: MC
authors.lastname: Kullberg
authors.forename: S
authors.initials: S
authors.lastname: Barbieri
authors.forename: P
authors.initials: P
authors.lastname: Caspar
authors.forename: J A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: R A
authors.initials: RA
authors.lastname: Seder
authors.forename: A
authors.initials: A
authors.lastname: Sher
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D015847:Interleukin-4 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D017455:Receptors, IgE / Q000032:analysis*; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013154:Spleen / Q000378:metabolism
chemical_list: D000947:Antigens, Helminth; D015848:Interleukin-5; D017455:Receptors, IgE; D015847:Interleukin-4