Principles of Clinical Pathology
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
A few animals will develop hematopoietic neoplasia, with or without leukemia, in most rodent carcinogenicity studies. Standard histopathology is superior to periodic or terminal hematologic evaluation for identification of hematopoietic neoplasia. Although some affected animals have markedly elevated total WBC count and circulating neoplastic cells (e.g., blasts), many animals do not. Lymphocytic leukemia is the most commonly observed leukemia in laboratory rats and is occasionally observed as an incidental finding in subchronic studies (Frith et al. 1993). Large granular lymphocyte leukemia (also called mononuclear cell leukemia) is a relatively common finding in older Fischer 344 rats (Stromberg 1985). Affected rats often develop an immune-mediated hemolytic anemia with increased total bilirubin and liver enzyme activities. In peripheral blood, neoplastic cells appear as large, immature lymphocytes, frequently containing prominent azurophilic granules.
Basic Knowledge of Host Defenses Against Infection
M. T. Labro in Host Defense and Infection, 1994
NK cells are a discrete subset of lymphocytes distinct from B and T cells, which lack antigen-recognition molecules (T cell receptor [TCR]) and surface immunoglobulins. LAK cells are a subset of NK which, upon activation by lymphokines (interleukin-2 [IL-2]), are able to kill several target cells. They derive from the lymphoid stem cell in the bone marrow, mostly have the large granular lymphocyte morphology, but kill a variety of target cells in a MHCnon-restricted fashion. NK cells have functions other than simple spontaneous cytotoxicity and regulate several cell types.
Specific Host Restance: The Effector Mechanisms
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
Natural killer (NK) cells are a distinct class of lymphocytes that do not fit into either the T cell or B cell categories. Because they lack surface immunoglobulins, TCRs, and other distinctive markers of the T or B cells, they are also referred to as null cells. NK cells possess large cytoplasmic granules that resemble those of the granular leukocytes. Because of this attribute, another name given to the natural killer cell is large granular lymphocyte. NK cells comprise five to ten percent of the circulating lymphocyte population in humans.
Choroidal Infiltration as First Clinical Manifestation of T-cell Large Granular Lymphocyte (T-LGL) Leukemia
Published in Ocular Immunology and Inflammation, 2020
Stephanie Sarny, Christine Beham-Schmid, Yosuf El-Shabrawi
Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disease of cytotoxic lymphoid cells. LGLs are T-lymphocytes or natural killer (NK) cells with three LGL subtypes, namely T-LGL leukemia, aggressive NK-cell leukemia, and chronic NK-cell lymphocytosis.1 They are characterized by the accumulation of cytotoxic cells in the blood with infiltration of the bone marrow, the spleen or the liver. T-LGL leukemia is extremely rare with an incidence of 0.2 patients per one million people.2 Men and women are equally affected with a median age of 66 years at diagnosis. A mutation in the STAT3 gene was identified as a recurrent genetic abnormality.3 T-LGL leukemia is associated with lymphocytosis, neutropenia and sometimes anemia and slight thrombocytopenia. Recurrent infections of the upper respiratory due to neutropenia and splenomegaly are the most common clinical manifestations. B-symptomatic is rare and half of the patients are even asymptomatic. Therefore, T-LGL leukemia is primary an indolent disease and some patients do not require systemic therapy over years. However, the disease is frequently associated with autoimmune disorders. Rheumatoid arthritis in up to one-third of all patients is the most common; others are systemic lupus erythematosus, vasculitis or Sjogren syndrome.
Dysfunction of immune system in the development of large granular lymphocyte leukemia
Published in Hematology, 2019
Houfang Sun, Sheng Wei, Lili Yang
Large granular lymphocyte (LGL) leukemia is identified as a rare type of lymphoproliferative disorder that results from the clonal expansion of large granular lymphocytes (LGLs) [1–6]. As key innate immune effectors, LGLs occupy roughly 10–15% of the peripheral blood mononuclear cells (PBMCs) and originate from two main lineages, CD3+ cytotoxic T-lymphocytes (CTLs) and CD3- natural killer (NK) cells [7–10]. In 2008, a provisional entity of chronic NK-cell lymphoproliferative disorder (CLPD-NK) was recognized by the WHO in order to distinguish it from the aggressive NK-cell leukemia. Thus there are three kinds of LGL disorders, namely T-cell large granular lymphocyte (T-LGL) leukemia, aggressive NK-cell leukemia and CLPD-NK [1,11,12]. The latest 2016 WHO guidelines followed the previous classification method, but specially underlined the detection of STAT mutations as a new subtype [11,13]. In fact, LGL leukemia can be considered as a result of the clonal expansion of either NK cells or T cells [2]. The abnormal proliferation of LGLs contributes to the development and progression of the immune system disorders in humans [8], including the autoimmune diseases, hematological abnormalities, and dysregulated signal transduction of T cells and NK cells, besides the B-cell dyscrasias. Consequently, LGL leukemia is an excellent model for the study of hematological cancers that manifest immune system dysregulations. Herein we mainly focus on the impaired homeostasis of the immune system in LGL leukemia and briefly introduce the novel therapeutic agents targeting the corresponding abnormalities in LGL leukemia.
Increased Peripheral NKG2A-NKG2D+CD3-CD16+CD56dim NK Cell Subset Was Positively Correlated with Antiphospholipid Antibodies in Patients of Obstetric Antiphospholipid Syndrome
Published in Immunological Investigations, 2022
Yinmei Zhang, Yang Zhao, Wenzhe Si, Boxin Yang, Mingmei Lin, Jiajia Zheng, Liyan Cui
Human NK can be subdivided into two main cell populations. About 90% are cytotoxic CD3−CD16+CD56dim NK cells, while the remaining 10% are non-cytotoxic CD3−CD16−CD56bright NK cells (Domaica et al. 2012). The CD56 + T cells (define as CD3+CD56+) comprise 5–15% of peripheral circulating T cells in human and express the typical NK cell surface marker CD56. CD56+T cells are also characterized by some NK cell-like properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells. The gating strategies of CD3−CD16+CD56dim NK cells, CD3−CD16−CD56bright NK cells and CD56+T cells are shown in Figure 1. We first compared the expression of these subsets in OAPS patients and healthy controls. The percentages of CD3−CD16+CD56dim and CD3−CD16−CD56bright NK cells in OAPS patients in higher than healthy control but not there was no statistical significance (p = .934, p = .651, respectively), CD56+T cells in OAPS patients in significantly higher than healthy control group (p = .03) (Figure 1b)