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
I Bank, M Book, L Cohen, A Kneller, E Rosental, M Pras, IB Bassat and A Ben-Nun
Dept. Medicine F, Sheba Medical Center, Tel-Hashomer, Israel.
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.
Volume 80,
Issue 12,
pp. 3157-3163,
12/15/1992
Copyright © 1992 by The American Society of Hematology
