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-p resenting dendritic cells were cultured with T cells using a 20-mul ha nging drop system. T cells from all subgroups of CVID patients showed markedly reduced responses to the recall antigens purified protein der ivative (PPD) or tetanus toxoid, whereas responses by cells from patie nts with X-linked agammaglobulinaemia, used as a disease control, were in the normal range. However, primary allo-stimulation of CVID T cell s was normal. CVID cells from two patients failed to respond to stimul ation with a neoantigen, an HIV env peptide, under conditions where no rmal T cells did respond. These data illustrate a profound defect in a ntigen-stimulated T cell proliferation in vitro in all groups of CVID patients, but do not distinguish whether the defect is in the presenti ng cell or in the T lymphocyte. In vivo, germinal centre B cells are t hought to present antigen to primed T cells to obtain essential signal s (e.g. CD40 ligand and IL-2) for B cell survival and progression to i mmunoglobulin 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 immu noglobulin production in this condition.