title: Lack of specific antibody response in common variable immunodeficiency (CVID) associated with failure in production of antigen-specific memory T cells. MRC Immunodeficiency Group.
abstract: Several T cell defects have been described in the antibody deficiency disease, CVID, but there have been few data on the generation of responses of specific T cell populations to primary neoantigens. We have now used immunization with the neoantigens, keyhole limpet haemocyanin (KLH) and DNP-Ficoll, to evaluate immune responses in CVID patients and normal donors. B and T cell responses were examined 2 and 4 weeks post-immunization. Sera were examined for IgM and IgG anti-KLH responses by ELISA and for anti-DNP-Ficoll activity by haemagglutination. The frequency of KLH-responsive T cells was measured by DNA synthesis in a limiting dilution culture system. Low density cells enriched for dendritic cells were pulsed with KLH and cultured with different numbers of autologous T cells. T cells from normal donors and from patients showed a low frequency of antigen-specific precursor T cells (< or = 1:200,000). After KLH immunization the frequency increased in normal donors (1:60,000 and 1:30,000 at 2 and 4 weeks, respectively), while in CVID patients it did not change from the pre-immunization level. The defect may extend to a dysfunction of antigen-specific cells, rather than being solely due to the reduced numbers of cells, since mean responses of 'positive' wells were also reduced. The serum-specific antibody response paralleled the T cell data, in that all normal donors but none of the CVID patients generated IgG KLH-specific antibodies. CVID patients did produce IgM antibodies against the T-independent DNP-Ficoll, but at a lower level than normal controls. These data show that both T and B cells from CVID patients have defective responses to specific antigen, implicating both lineages in the antibody deficiency.
authors.affiliation: Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Kondratenko
authors.forename: P L
authors.initials: PL
authors.lastname: Amlot
authors.forename: A D
authors.initials: AD
authors.lastname: Webster
authors.forename: J
authors.initials: J
authors.lastname: Farrant
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000276:immunology*; D005260:Female; D005362:Ficoll / Q000031:analogs & derivatives* / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007156:Immunologic Memory / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; C031007:DNP-Ficoll; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D005362:Ficoll; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin