Failure in antigen responses by T ceils from patients with common variable immunodeficiency (CVID)


John Farrant, MRC Immunodeficiency Research Group, Department of Clinical Immunology, Royal Free Hospital School of Medicine, Pond St. London NW3 2QG. UK.


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-μl hanging drop system, T cells from all subgroups of CVID patients showed markedly reduced responses lo 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 lo respond to stimulation with a neoantigen, an HIV env peptide. under conditions where normal T ceils 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 vitro, germinal centre B cells are thought lo present antigen to primed T cells lo 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.