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Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Human filarial helminth infections are characterized by type 2
immune responses to parasite Ag that can persist for the life of the
individual; one possible cause for this may be prenatal exposure to the
blood-borne microfilarial (Mf) stage of the parasite. To examine the
relationship between early exposure to filarial Ag and subsequent
immune responsiveness, CD45RA+CD4+ cells
from normal unsensitized donors were stimulated in vitro with soluble
microfilarial Ag (MfAg) from the filarial parasite Brugia
malayi in the presence of APCs. MfAg alone induced proliferation
and IFN-
and IL-5 production in unsensitized
CD45RA+CD4+ cells, demonstrating the ability of
filarial Ags to prime naive T cells in the absence of exogenous
cytokines and dendritic cells. Adding exogenous cytokine(s)
(particularly IL-12 and IL-4) during priming was able to alter the
MfAg-specific responses of CD45RA+CD4+ cells as
well as subsequent responses to Ag. Interestingly, priming solely with
MfAg led to enhanced IL-5 production following Ag restimulation,
suggesting that MfAg preferentially primes for type 2 responses. These
data demonstrate that filarial Ags by themselves can specifically prime
CD45RA+CD4+ cells in vitro and do so in such a
way as to deviate the immune response.
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