Relative increase of T cells expressing the gamma/delta rather than the alpha/beta receptor in ataxia-telangiectasia.
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: alpha/beta chains on mature cells and gamma/delta 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 gamma/delta receptors rather than alpha/beta receptors, as compared with normal subjects (P less than 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 gamma/delta-bearing to alpha/beta-bearing cells. A marked predominance of gamma/delta-bearing T cells was found in a patient with a primary T-cell defect. The relative increase in gamma/delta-bearing 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 C gamma 1 gene product of the T-cell receptor. Although they had normal ratios of gamma/delta-bearing to alpha/beta-bearing T cells, the patients with common variable immunodeficiency had a significant increase (P = 0.01) in the number of T cells expressing C gamma 2 that reacted with the monoclonal antibody delta-TCS-1. We conclude that the increased ratio of gamma/delta-bearing to alpha/beta-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.
Carbonari
M
M
Department of Clinical Immunology, University of Rome, La Sapienza, Italy.
Cherchi
M
M
Paganelli
R
R
Giannini
G
G
Galli
E
E
Gaetano
C
C
Papetti
C
C
Fiorilli
M
M
D000293:Adolescent; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000276:immunology*; D017252:CD3 Complex; D002648:Child; D002675:Child, Preschool; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology; D007073:Immunoglobulin E / Q000032:analysis; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000276:immunology*; D013601:T-Lymphocytes / Q000032:analysis / Q000276:immunology*; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D007073:Immunoglobulin E