Prenatal T cell immunity to Wuchereria bancrofti and its effect on filarial immunity and infection susceptibility during childhood.
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.


CONCLUSIONS
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.
Malhotra
Indu
I
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio 44106-7286, USA.
Mungai
Peter L
PL
Wamachi
Alex N
AN
Tisch
Daniel
D
Kioko
John M
JM
Ouma
John H
JH
Muchiri
Eric
E
Kazura
James W
JW
King
Christopher L
CL
D000818:Animals; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D005368:Filariasis / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13; D007376:Interleukin-2 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D018512:Parasitemia; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014958:Wuchereria bancrofti / Q000276:immunology*
D018793:Interleukin-13; D007376:Interleukin-2; D015848:Interleukin-5; D007371:Interferon-gamma