In ataxia—telangiectasia, B-cell and T-cell deficiencies are thought to be due to a defect of rearrangements of immunoglobulin and T-cell receptor genes. T cells recognize antigens through two types of CD3-associated receptors: α/β chains on mature cells and γ/δ chains mostly on immature cells.

We studied 10 patients with ataxia—telangiectasia and found that most had a relative increase of circulating T cells bearing γ/δ receptors rather than α/β receptors, as compared with normal subjects (P<0.001). Patients with other immune deficits, including eight with common variable immunodeficiency, one with Wiskott—Aldrich syndrome, two with hyperimmunoglobulinemia E syndrome, and one with severe combined immunodeficiency, had normal ratios of γ/δ-bearing to α/β-bearing cells. A marked predominance of γ/δ-bearing T cells was found in a patient with a primary T-cell defect. The relative increase in γ/δbearing T cells in the patients with ataxia—telangiectasia was largely accounted for by cells that reacted with the monoclonal antibody BB3, an apparently distinct subset of T cells that selectively express the Cγ1 gene product of the T-cell receptor. Although they had normal ratios of γ/δbearing to α/β-bearing T cells, the patients with common variable immunodeficiency had a significant increase (P = 0.01) in the number of T cells expressing Cγ2 that reacted with the monoclonal antibody δ-TCS-1.

We conclude that the increased ratio of γ/δ-bearing to α/β-bearing T cells in ataxia—telangiectasia may reflect both a recombinational defect that interferes with T-cell and B-cell gene rearrangements and an inability to repair damage to the DNA. (N Engl J Med 1990; 322:73–6.)