title: Defects in antigen-driven lymphocyte responses in common variable immunodeficiency (CVID) are due to a reduction in the number of antigen-specific CD4+ T cells.
abstract: T cells from patients with CVID have defects that may relate to the failure in vivo of B cell production of antibodies. Antigen-driven responses of T cells from CVID patients and normal subjects have been assessed by measuring DNA synthesis in vitro. Low density cells enriched for antigen-presenting dendritic cells were pulsed with purified protein derivative (PPD) and cultured with autologous T cells. Overall, T cells from CVID patients showed a significantly low mean response to PPD, although non-specific DNA synthesis induced in CVID T cells by IL-2 was within the normal range. However, mean PPD-specific T cell responses in CVID were not restored by IL-2 irrespective of the presence of monocytes. Depletion of CD8+ cells also failed to restore the mean PPD response of CVID CD4+ T cells. Limiting dilution analysis showed that in CVID there was a reduced frequency of antigen-specific cells within the T cell preparations. The mean frequency of the PPD-specific T cells in cultures from patients vaccinated with bacille Calmette-Guérin (BCG) was reduced to 1 in 109,000 T cells compared with 1 in 18,600 T cells in BCG-vaccinated normal donors. These data show that the reduced PPD-specific response in CVID is due to a partial peripheral loss of antigen-specific cells.
authors.affiliation: Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Funauchi
authors.forename: J
authors.initials: J
authors.lastname: Farrant
authors.forename: C
authors.initials: C
authors.lastname: Moreno
authors.forename: A D
authors.initials: AD
authors.lastname: Webster
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D014373:Tuberculin / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D014373:Tuberculin