Role of IL-10 on antigen-presenting cell function for schistosomal egg-specific monoclonal T helper cell responses in vitro and in vivo.
Egg Ag-stimulated lymphoid cell culture supernatants from schistosome-infected mice significantly inhibited Ag-specific, MHC-restricted proliferative responses of cloned schistosomal egg Ag-specific CD4+, Th-1-type lymphocytes. The inhibitory molecule in the supernatants was found to be the cytokine IL-10. Maximal IL-10 was produced by cells from mice carrying 8-wk schistosome infections, and none by cells from normal mice. IL-10 exerted its biologic activity on APC, and not directly on the cloned lymphocytes, resulting in the inhibition of Th-1 lymphocyte proliferation, whereas Th-2 responses were not affected. Most significantly, IL-10 also affected Th-1 clone activity in vivo, as measured by the inhibition of schistosomal egg Ag-specific local delayed-type hypersensitivity reactions. IL-10 produced in schistosome-infected individuals may play a role in the generation of APC, such as macrophages in schistosomal egg granulomas, unable to efficiently stimulate, but capable of inducing a state of anergy/unresponsiveness in Th-1 lymphocytes. We believe that this state of Th-1 cell anergy translates into the down-regulation of granulomatous hypersensitivity (immunomodulation) characteristically observed in the evolving schistosomal disease.
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.
P O
PO
Flores Villanueva
S M
SM
Chikunguwo
T S
TS
Harris
M J
MJ
Stadecker
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000947:Antigens, Helminth / Q000276:immunology*; D005260:Female; D015801:Helminth Proteins; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016753:Interleukin-10 / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D012550:Schistosoma mansoni / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000947:Antigens, Helminth; D015801:Helminth Proteins; C055560:p40 egg antigen, Schistosoma; D016753:Interleukin-10