Expansion of a unique subpopulation of cytotoxic T cells that express a C alpha V delta 1 T-cell receptor gene in a patient with severe persistent neutropenia.
CD8+ T-lymphocyte populations may be expanded in the peripheral blood of patients with chronic idiopathic neutropenia and may be involved in suppression of granulopoiesis. In this report, we have analyzed the T-cell receptor (TCR) used by the T lymphocytes of a patient with chronic severe neutropenia. Using specific oligonucleotides in the polymerase chain reaction (PCR) to amplify cDNA specific for the different families of the V alpha, V beta, and V delta TCR genes, and monoclonal antibodies (MoAbs) to examine T-lymphocyte subsets and their TCR, a persistent expansion of CD3+CD8+ T lymphocytes and a reduced repertoire of TCR V alpha and V beta genes were found in the patient's peripheral blood mononuclear cell (PBMC) preparations. A predominant portion of the T lymphocytes expressed a unique TCR structure. Thus, we found that, despite the fact that 98% of the T cells expressed alpha beta TCR on the surface membrane and less than 2% expressed tau delta TCR, nonetheless, 40% to 60% of the T cells stained positively with anti V delta 1 MoAb. Using the PCR analysis, the V delta 1 gene segment was found to be rearranged to C alpha, rather than to C delta genes. The expanded C alpha V delta 1+ cells, which are found only rarely in normal PB, expressed CD8 and were cytotoxic, and the C alpha V delta 1 receptor was functional in cytotoxicity. This constitutes the first description of an expansion of cytotoxic CD8+ lymphocytes expressing a functional "hybrid" C alpha V delta 1 gene in vivo, and suggests a pathogenic role for CD8+ C alpha V delta 1+ cells in some patients with idiopathic neutropenia.
Bank
I
I
Dept. Medicine F, Sheba Medical Center, Tel-Hashomer, Israel.
Book
M
M
Cohen
L
L
Kneller
A
A
Rosental
E
E
Pras
M
M
Bassat
I B
IB
Ben-Nun
A
A
D000911:Antibodies, Monoclonal; D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009503:Neutropenia / Q000097:blood / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology / Q000473:pathology; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000235:genetics*; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D009838:Oligodeoxyribonucleotides; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta