The Journal of infectious diseases · 2006
Prenatal T cell immunity to Wuchereria bancrofti and its effect on filarial immunity and infection susceptibility during childhood.
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Malhotra Indu, Mungai Peter L, Wamachi Alex N, Tisch Daniel, Kioko John M, Ouma John H, Muchiri Eric, Kazura James W, King Christopher L
Аннотация
BACKGROUND: Antenatal immune experience with Wuchereria bancrofti due to maternal filariasis may influence susceptibility to infection. We tested the hypothesis that filarial-specific T cell responses at birth that are indicative of in utero tolerance or sensitization affect the evolution of filarial-specific immunity and susceptibility to W. bancrofti infection during childhood.
METHODS: A birth-cohort study of 159 Kenyan newborns was performed. Cord blood and peripheral blood were obtained annually to age 7 years and were assayed for filarial infection and filarial antigen-driven interferon (IFN)- gamma , interleukin (IL)-2, IL-5, and IL-13 production by lymphocytes.
RESULTS: There was a 12.9-fold (95% confidence interval [CI], 2.5-107.2-fold) and a 4.8-fold (95% CI, 1.7-12.9-fold) increased risk of infection for immune-tolerant newborns (maternal infection present during gestation, with no filarial antigen-driven cord blood T cell response [n = 25]), compared with immune-sensitized (maternal infection present with cord blood T cell response [n = 24]) and unexposed (maternal infection absent [n = 110]) newborns. Cytokine responses developed at a later age in tolerant newborns, were characterized by impaired IFN-gamma responses, and contrasted with those of filarial-sensitized newborns, who had sustained and elevated IL-5 and IL-13 responses to age 7 years.
CONCLUSION: Prenatal immune experience, as determined by whether in utero priming to filarial antigen occurs, is a major determinant of childhood susceptibility to W. bancrofti infection.
METHODS: A birth-cohort study of 159 Kenyan newborns was performed. Cord blood and peripheral blood were obtained annually to age 7 years and were assayed for filarial infection and filarial antigen-driven interferon (IFN)- gamma , interleukin (IL)-2, IL-5, and IL-13 production by lymphocytes.
RESULTS: There was a 12.9-fold (95% confidence interval [CI], 2.5-107.2-fold) and a 4.8-fold (95% CI, 1.7-12.9-fold) increased risk of infection for immune-tolerant newborns (maternal infection present during gestation, with no filarial antigen-driven cord blood T cell response [n = 25]), compared with immune-sensitized (maternal infection present with cord blood T cell response [n = 24]) and unexposed (maternal infection absent [n = 110]) newborns. Cytokine responses developed at a later age in tolerant newborns, were characterized by impaired IFN-gamma responses, and contrasted with those of filarial-sensitized newborns, who had sustained and elevated IL-5 and IL-13 responses to age 7 years.
CONCLUSION: Prenatal immune experience, as determined by whether in utero priming to filarial antigen occurs, is a major determinant of childhood susceptibility to W. bancrofti infection.