MALIGNANT CLONAL EXPANSION OF LARGE ANTIGRANULOCYTES LYMPHOCYTES WITH A LEU-11+, LEU-7 - SURFACE PHENOTYPE - INVITRO RESPONSIVENESS OF MALIGNANT-CELLS TO RECOMBINANT HUMAN INTERLEUKIN-2

  • 1 November 1986
    • journal article
    • research article
    • Vol. 68  (5) , 1065-1073
Abstract
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. lmymphocytes. 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 antigne under the influence of IL 2 administration, followed by remarkable cell proliferation and .gamma.-IFN production.

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