TY - JOUR
T1 - 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
AU - Hoffmann, K F
AU - James, S L
AU - Cheever, A W
AU - Wynn, T A
N1 - Hoffmann, K. F., James, S. L., Cheever, A. W., Wynn, T. A. (1999). 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. Journal of Immunology, 163 (2), 927-938
PY - 1999/7/15
Y1 - 1999/7/15
N2 - 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-γ- 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.
AB - 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-γ- 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.
UR - http://www.scopus.com/inward/record.url?scp=0033566010&partnerID=8YFLogxK
M3 - Article
C2 - 10395689
SN - 0022-1767
VL - 163
SP - 927
EP - 938
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -