Failure in antigen responses by T cells from patients with common variable immunodeficiency (CVID).
Antigen-driven responses by T cells from patients with CVID and normal subjects have been assessed. Low-density cells enriched for antigen-presenting dendritic cells were cultured with T cells using a 20-microliters hanging drop system. T cells from all subgroups of CVID patients showed markedly reduced responses to the recall antigens purified protein derivative (PPD) or tetanus toxoid, whereas responses by cells from patients with X-linked agammaglobulinaemia, used as a disease control, were in the normal range. However, primary allo-stimulation of CVID T cells was normal. CVID cells from two patients failed to respond to stimulation with a neoantigen, an HIV env peptide, under conditions where normal T cells did respond. These data illustrate a profound defect in antigen-stimulated T cell proliferation in vitro in all groups of CVID patients, but do not distinguish whether the defect is in the presenting cell or in the T lymphocyte. In vivo, germinal centre B cells are thought to present antigen to primed T cells to obtain essential signals (e.g. CD40 ligand and IL-2) for B cell survival and progression to immunoglobulin secretion. A failure of antigen-specific T cell function in vivo in CVID would thus not provide the primed T cells needed for B cell rescue, and could be the primary defect leading to the low immunoglobulin production in this condition.
Stagg
A J
AJ
Antigen Presentation Group, Clinical Research Centre, Harrow, UK.
Funauchi
M
M
Knight
S C
SC
Webster
A D
AD
Farrant
J
J
D000938:Antigen-Presenting Cells / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
D007519:Isoantigens; D013745:Tetanus Toxoid; D014373:Tuberculin