Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes

Abstract

Two major types of lymphocytosis of large granular lymphocytes (LGLs) were observed. The proliferating LGLs in each type had distinct immunophenotypes, functional characteristics, and probably belonged to different cell lineages. The more common form (Type A) consisted of cells derived from the T cell lineage and had the T suppressor/cytotoxic phenotype (T11+, T3+, T8+). The expression of the Leu 7 and HLA-DR antigen was variable. These cells did not have natural killer (NK) function but showed a variable degree of antibody-dependent cell-mediated cytotoxic (ADCC) activity. Neutropenia was invariably present and rheumatoid arthritis and autoantibodies were frequent associations. These lymphocytes had many similarities to the major type of LGLs present in normal adult bone marrow. The other type of LGL lymphocytosis (Type B) consisted of cells lacking the antigens T3 and T8 but expressing M1 and NKH1. These cells possessed strong NK and ADCC activity but their cell lineage was not clear. Neutropenia and autoimmune phenomena were not detected. The cytochemical characteristics of the LGL granules from both types of patients were similar but differences in ultrastructure were observed. LGLs from Type B patients proliferated in the presence of Interleukin 2 (IL-2) and 12- O-tetradecanoyl-phorbol-13 acetate (TPA). Significant changes in their basic T11+, T3-, T8- phenotype were not observed. IL-2 and TPA, however, had profound influence on the NK function of the cells with enhancement in the case of IL-2 and marked suppression when stimulated by TPA.

A long‐term study of patients with chronic natural killer cell lymphocytosis

“…Another major difference between our patients with CNKL and those with T-LGL leukaemia was that 26% of patients with T-LGL leukaemia but only 6% with CNKL had rheumatoid arthritis. The close association between T-LGL leukaemia and rheumatoid arthritis is well established (Loughran & Starkebaum, 1987), but not between rheumatoid arthritis and CNKL (Chan et al, 1986(Chan et al, , 1992Oshimi et al, 1993). In addition to rheumatoid arthritis, patients with T-LGL leukaemia often have laboratory and clinical evidence of autoimmune phenomena (Dhodapkar et al, 1994b;Gentile et al, 1996).…”

Biology of Natural Killer Cells

“…These cells have phenotypic and functional characteristics identical to those of peripheral blood NK cells. Chan et al (437) observed that nine patients with CD3+…”

Evaluation of serum levels of soluble interleukin-2 receptor in patients with chronic lymphoproliferative disorders of T-lymphocytes

“…'6, 24-'5 Two distinct groups of LDGL patients may be recognized on the basis of the expression of CD3 antigen and T-cell receptor. 26 The larger group is characterized by cases in which proliferating cells express CD3 determinants and display low NK activity. In the second group of patients, GL are CD3-and display higher NK activity in vitro.…”