Studies with double cytokine-deficient mice reveal that highly polarized Th1- and Th2-type cytokine and antibody responses contribute equally to vaccine-induced immunity to Schistosoma mansoni.
A fundamental obstacle to vaccine development in schistosomiasis mansoni is a lack of understanding of what type of an immune response should be invoked. We have addressed this central issue by using the radiation-attenuated cercariae vaccine in mice genetically engineered to exhibit highly polarized type 1 (IL-10/IL-4-deficient) or type 2 (IL-10/IL-12-deficient) cytokine and Ab phenotypes. Our data show that while significant differences in immunity exist after a single vaccination with irradiated cercariae in double cytokine-deficient vs wild-type mice, these differences disappear after two vaccinations. The most important finding of these studies, however, was revealed in vaccinated IL-10-deficient mice. These mice developed a mixed and elevated type 1- and type 2-associated immune response and developed anti-schistosome immunity at levels equal to or better than those in wild-type mice. This immunity in IL-10-deficient mice correlated with higher parasite-specific Ab titers, greater proliferative capacity of lymphocytes, increased frequency of IFN-gamma- and IL-4-secreting cells, elevated perivascular/peribronchial inflammatory responses in the lung, and greater in vitro schistosomulacidal capacity of parasite Ag-elicited cells. These results suggest that optimal vaccine-induced immunity against schistosomes is linked not to the development of a highly polarized response, but, rather, to the induction of both type 1- and type 2-associated immune responses.
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
K F
KF
Hoffmann
S L
SL
James
A W
AW
Cheever
T A
TA
Wynn
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis*; D000947:Antigens, Helminth / Q000276:immunology; D001980:Bronchi / Q000098:blood supply / Q000469:parasitology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D007111:Immunity, Cellular / Q000235:genetics; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D007814:Larva / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000469:parasitology / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D014613:Vaccines, Attenuated; D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma