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Malignant clonal expansion of large granular lymphocytes with a Leu- 11+,
Leu-7- surface phenotype: in vitro responsiveness of malignant cells to
recombinant human interleukin 2
S Koizumi, H Seki, T Tachinami, M Taniguchi, A Matsuda, K Taga, T Nakarai, E Kato, N Taniguchi and H Nakamura
A 14-year-old Japanese female with neutropenia showed malignant
proliferation of the large granular lymphocytes (LGLs). These LGLs were E
rosette+ and Fc(IgG) receptor+ and therefore are referred to as T gamma
lymphocytes. They were also Leu-11+ and OKT11+; however, they were clearly
negative for Leu-7, OKT3, OKT8, OKM1, and HNK-1 antigens as well as for
terminal deoxynucleotidyl transferase activity. Karyotype analysis revealed
47, XXX. The LGLs showed no rearrangement of T cell receptor C beta genes.
The natural killer (NK) cell activity against K562 target cells was low,
but was significantly augmented after stimulation by recombinant human
interleukin 2 (IL 2) in contrast to minimal NK boosting by recombinant
human gamma-interferon (gamma- IFN). Such a unique responsive ability to
lymphokines was quite similar to that noted in fetal and cord blood cells.
These LGLs also demonstrated a considerable increase in antibody-dependent
cell- mediated cytotoxicity (ADCC) and lymphokine-activated killer (LAK)
activity after a short incubation with IL 2. Although in a resting stage
they showed no IL 2 receptor expression as examined by anti-Tac antibody,
Tac antigen appeared after IL 2 treatment followed by a marked increase in
3H-thymidine incorporation and a remarkable production of gamma-IFN. To
investigate the mechanism of neutropenia, in vitro IL 2-stimulated
coculture studies of these cells with normal bone marrow cells were
performed. Colony formation of myeloid progenitors (CFU-C) was
significantly suppressed. In addition, the conditioned medium from IL
2-stimulated LGLs indicated a remarkable suppression of CFU-C. These
results suggest that these LGLs with a Leu- 11+, Leu-7- surface phenotype
might belong to a unique subset of pre-NK cells that are functionally and
phenotypically similar to those represented at any early stage of human
ontogeny and that they strongly express Tac antigen under the influence of
IL 2 administration, followed by remarkable cell proliferation and
gamma-IFN production.
Volume 68,
Issue 5,
pp. 1065-1073,
11/01/1986
Copyright © 1986 by The American Society of Hematology
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