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Division of Geographic Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106;
Veterans Affairs Medical Center, Cleveland, OH 44106; and
Papua New Guinea Institute of Medical Research, Goroka and Madang, Papua New Guinea
Humans living in areas where filariasis is endemic vary greatly in
their exposure to mosquito-borne infective third-stage larvae
(L3) of these parasitic helminths. Because the intensity of exposure to
Ags affects T cell differentiation and susceptibility to parasitic
infections in murine models, we compared T cell and cytokine responses
in 97 residents of two villages in Papua New Guinea, where transmission
intensity of Wuchereria bancrofti differed by 63-fold
(37 vs 2355 L3 per person per year). Residents of the high transmission
village had 4- to 11-fold lower proliferation and IFN-
responses to
filarial Ags, nonparasite Ag, and PHA by PBMC compared with the low
transmission village (p < 0.01) even when subjects
were matched for intensity of infection. In contrast, filarial
Ag-driven IL-5 production was 5.5-fold greater (p
< 0.001), and plasma IL-4 and TGF-
levels were 4-fold and 34%
higher, respectively, in residents of the high transmission village.
IL-4 and IL-10 responses by PBMC differed little according to village,
and increased production of the counterregulatory cytokines IL-10 or
TGF- by PBMC did not correlate with weak proliferation and IFN-
responses. Plasma IL-5, IFN-, and IL-10 levels were similar in the
two villages. These data demonstrate that the intensity of exposure to
L3 affects lymphocyte responsiveness and cytokine bias possibly
by a mechanism that alters APC function.
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