Expansion of a unique subpopulation of cytotoxic T cells that express a CαVδ1 T-cell receptor gene in a patient with severe persistent neutropenia

Abstract

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 Vα, Vβ, and Vδ 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 Vα and Vβ 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 αβ TCR on the surface membrane and less than 2% expressed τδ TCR, nonetheless, 40% to 60% of the T cells stained positively with anti Vδ1 MoAb. Using the PCR analysis, the Vδ1 gene segment was found to be rearranged to Cα, rather than to Cδ genes. The expanded CαVδ1+ cells, which are found only rarely in normal PB, expressed CD8 and were cytotoxic, and the CαVδ1 receptor was functional in cytotoxicity. This constitutes the first description of an expansion of cytotoxic CD8+ lymphocytes expressing a functional "hybrid" CαVδ1 gene in vivo, and suggests a pathogenic role for CD8+ CαVδ1+ cells in some patients with idiopathic neutropenia. © 1992 by The American Society of Hematology.