T gamma-lymphoproliferative disease and related disorders in humans and experimental animals: a review of the clinical, cellular, and functional characteristics

Abstract

T gamma lymphocytes are those lymphocytes that express receptors for both the Fc portion of IgG and sheep erythrocytes. A very high proportion of normal T gamma lymphocytes are large granular lymphocytes (LGL), the cell responsible for most, if not all, natural killer (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) in humans, rats, and mice. In general, these cells are large lymphocytes with prominent azurophilic granules in the cytoplasm. Recently, a group of lymphoproliferative disorders made up predominantly of T gamma lymphocytes has been described. The most common and best studied of these disorders we refer to as “chronic T gamma-lymphoproliferative disease” (T gamma-LPD). In most cases, this disease represents the abnormal expansion of LGL, which is reflected by an increase in functionally active NK or ADCC effector cells. The chronic T gamma-LPD lymphocytes are generally characterized as E- and EA-rosette positive, acid-phosphatase, and beta-glucuronidase positive and express the pan-T antigens OKT3/Leu-4, OKT11/Leu-5, the suppressor-associated antigens OKT5,8/Leu-2, and the NK-associated antigens Leu-7/HNK-1. Typically, the patients are older, predominantly males and characteristically have a lymphocytosis of predominantly T gamma lymphocytes with lymphocyte infiltration of the bone marrow and often the spleen. While chronic T gamma-LPD is not usually an aggressive disease, the patients are often neutropenic and have recurrent bacterial infections requiring antibiotic therapy. Some patients have benefited from cytotoxic chemotherapy., but most patients have not required chemotherapy. An experimental LGL leukemia in F344 rats appears morphologically, functionally, and clinically similar to the human chronic T gamma-LPD and serves as an experimental model for further examining the ontogeny and function of LGL and may be applicable for exploring new and more effective means for the treatment of patients with chronic T gamma-LPD.

Cyclophosphamide therapy for pure red cell aplasia associated with granular lymphocyte‐proliferative disorders

“…Cyclophosphamide was also effective for the neutropenia of patients 2, 3, 4 and 6. Neutropenia is seen in more than half of the patients with GLPD (Gastl et al, 1986;Newland et al, 1984;Reynolds & Foon, 1984), but the mechanism of neutropenia is not completely understood. Inhibition at the progenitor level seems unlikely, because, in our patients, neutrophils in the marrow were normal or rather hyperplastic.…”

Haemophagocytic lymphohistiocytosis in association with granular lymphocyte proliferative disorders in early childhood: characteristic bone marrow morphology

“…Secondary HLH has been reported in connection with proliferative disorders of large granular lymphocytes (LGL) in adults (Okuda et al, 1991;Kwong et al, 1995); however, this correlation has rarely been reported in young children. Granular lymphocyte proliferative disorders, GLPD (Oshimi, 1988;Loughran, 1993), are characterized mainly in adults by chronic or acutely aggressive proliferation of large lymphocytes with cytoplasmic azurophilic granules and has been variously reported as chronic T-gamma lymphoproliferative disease (Reynolds & Foon, 1984) or large granular lymphocyte leukaemia/lymphoma (LGLL; Loughran & Starkebaum, 1987;Kwong et al, 1995). This disorder has also been linked with natural killer (NK) cell leukaemia/lymphoma (Imamura et al, 1990;Hart et al, 1992).…”