title: Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.
abstract: To explore the mechanisms of antigen-specific immune unresponsiveness seen in microfilaremic patients with bancroftian filariasis, T and B cell precursor frequency analysis was performed using PBMC from individuals with either asymptomatic microfilaremia (MF, n = 7) or chronic lymphatic obstruction (CP, n = 20). Highly purified CD3+ cells were partially reconstituted with adherent cells and their proliferative response to parasite antigens determined in cultures of T cells by limiting dilution analysis. A filter immunoplaque assay also assessed the frequency of both total and parasite-specific Ig-producing B cells. While the lymphocyte proliferation to mitogens and to a nonparasite antigen (Streptolysin-O, [SLO]) were similar in all groups of patients, the frequency of parasite-specific CD3+ T cells was significantly lower (geometric mean [GM], 1/3,757) in MF patients when compared to that in CP patients (GM 1/1,513; P less than 0.001). Similarly, the proportion of lymphocytes producing parasite-specific IgE or IgG was significantly lower in MF patients (IgE mean, 0.2%; IgG mean, 0.33%) compared with CP patients (IgE mean, 3.2%; IgG mean, 1.76%; P less than 0.05 for both comparisons). These observations imply that low numbers of parasite-specific T and B lymphocytes may be partially responsible for the severely diminished capacity of lymphocytes from patients with MF to produce parasite-specific antibody and to proliferate to parasite antigen in vitro. Such differences in parasite-specific lymphocyte responses suggest that tolerance by clonal anergy may be a critical mechanism for maintaining the microfilaremic state.
authors.affiliation: Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: C L
authors.initials: CL
authors.lastname: King
authors.forename: V
authors.initials: V
authors.lastname: Kumaraswami
authors.forename: R W
authors.initials: RW
authors.lastname: Poindexter
authors.forename: S
authors.initials: S
authors.lastname: Kumari
authors.forename: K
authors.initials: K
authors.lastname: Jayaraman
authors.forename: D W
authors.initials: DW
authors.lastname: Alling
authors.forename: E A
authors.initials: EA
authors.lastname: Ottesen
authors.forename: T B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000947:Antigens, Helminth / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D002009:Brugia / Q000276:immunology; D004605:Elephantiasis, Filarial / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007074:Immunoglobulin G; D007073:Immunoglobulin E