TH1-LIKE ANTIFILARIAL IMMUNE-RESPONSES PREDOMINATE IN ANTIGEN-NEGATIVE PERSONS

To characterize immune responses associated with the putatively immune state in banecroftian filariasis (that is, both microfilaria and anti gen free), humoral and cellular responses were compared among antigen- and microfilatria-negative, antigen-positive and microfilaria-negativ e, and microfilaria-positive individuals. Antifilarial isotype levels were measured by enzyme-linked immunosorbent assay. Peripheral blood m ononuclear cell responses, were measured proliferation, by bioassay fo r interleukin 2 (IL-2) and IL-10, and by reverse transcription-PCR for IL-4, IL-5, and gamma interferon. The absence of circulating filarial antigen was associated with Th1-like responses, including significant ly higher proliferative (P < 0.001) and IL-2 (P = 0.008) responses and a higher prevalence of gamma interferon (0.02 < P < 0.1) responses. S ignificantly elevated antifilarial immunoglobulin G4 (IgG4) levels (P = 0.0035) were associated with antigenemia, whereas microfilaremia was associated with significantly decreased antifilarial IgG2 levels (P = 0.0014). IL-4 mRNA levels were not significantly different among the three groups; however, there mas a subpopulation of micro-filaremic in dividuals who did not make detectable levels of IL-4 mRNA and who prod uced low antifilarial IgG4 levels compared with those of individuals w ho had detectable levels of IL-4 mRNA. IL-5 mRNA levels also were not significantly different among groups; however, more microfilaremic ind ividuals produced IL-5 mRNA in response to adult filarial antigens, an d total parasite-specific IL-4 and IL-5 mRNA levels were significantly correlated (P = 0.05)). Although longitudinal data are not currently available, the elevated Th1-like responses in antigen- and microfilari a-negative individuals are consistent with the hypothesis that these r esponses contribute to protection in putatively immune individuals.