Monoclonal T-cell expansions in asymptomatic individuals and in patients with large granular leukemia consist of cytotoxic effector T cells expressing the activating CD94:NKG2C/E and NKD2D killer cell receptors

Article Article scientifique Article Monoclonal T-cell expansions in asymptomatic individuals and in patients with large granular leukemia consist of cytotoxic effector T cells expressing the activating CD94:NKG2C/E and NKD2D killer cell receptors eng 2003 author Bigouret Valérie Hélène 99501 author Hoffmann Till Peter Joseph 524681 author Arlettaz Lionel Aloïs Etienne 97577 author Villard Jean 29595 author Colonna Marco author Ticheli André author Gratwohl Alois 51279 author Samii Kaveh 24652 author Chapuis Bernard 24001 author Rufer Nathalie 28152 author Roosnek Eddy Emile 27236 3198-3204 10.1182/blood-2002-08-2408 12480700 0006-4971 We have analyzed the phenotype, cytokine profile, and mitotic history (telomere length) of monoclonal T-cell expansions in 5 CD3(+) T-cell large granular lymphocyte (TLGL) leukemia patients by fluorescence activated cell sorting (FACS) and single-cell polymerase chain reaction (PCR). We confirm that the common phenotype of TLGL leukemia is CD3(+)CD8(+)CD45RA(+)CD27(-)CD94(+)(CD57(+)). Interestingly, the C-type lectin-like type killer cell receptor CD94 was invariably associated with the activating form of its signal-transducing molecule NKG2. Furthermore, when judged by criteria such as interferon gamma (IFN-gamma)/tumor necrosis factor (TNF) production, expression of granzyme, FasL, and NKG2D, the TLGL cells had all the features of a cytotoxic effector T cell. Telomere shortening in TLGL cells was in the normal range for CD8(+) T cells, indicating that they had not divided significantly more than chronically stimulated CD8(+) T cells in healthy individuals. In 25 of 27 controls, cells with a TLGL phenotype occurred at low (1%-3%) frequencies. However, in the other 2 individuals (ages 28-36 years), large stable (> 3 years) monoclonal expansions of CD3(+)CD8(+)CD45RA(+)CD27(-)CD57(+)CD94(+) NKG2C(+) were found which rendered these controls phenotypically indistinguishable from TLGL leukemia patients. We believe that the TLGL clonopathy, rather than being of a neoplastic nature, is more likely an extreme manifestation of the large and stable clonal size characteristic of CD8(+) effector cells. Such a TLGL clone consisting of cells without any particular pathologic trait might exist in a considerable number of individuals. Clinical symptoms may occur in individuals in whom the TLGL clone encounters antigen and is triggered to produce large amounts of effector molecules that dysregulate the immune system, which could manifest itself as autoimmunity or as a FasL-mediated neutropenia. Antigens CD/analysis CD57 Antigens/analysis Cell Differentiation Clone Cells/chemistry/immunology Humans Immunophenotyping Lectins C-Type/analysis Leukemia T-Cell/immunology/pathology Leukocyte Common Antigens/analysis Lymphocyte Activation NK Cell Lectin-Like Receptor Subfamily C NK Cell Lectin-Like Receptor Subfamily D NK Cell Lectin-Like Receptor Subfamily K Neoplasm Proteins/analysis Receptors Immunologic/analysis Natural Killer Cell T-Lymphocyte Subsets/chemistry/immunology T-Lymphocytes Cytotoxic/chemistry/immunology Telomere/ultrastructure Dewey 616 Swiss National Science Foundation 3100-65′357.01 CH 56 Département de médecine 221 false 298 Transplantation immunologie et osteoimmunologie 561 Blood 101 8 b65e3bb5-6d82-4516-95e5-dab4e1d5dd50 Article (Published version) Public h80803003198.pdf 120604 application/pdf openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Monoclonal T-cell expansions in asymptomatic individuals and in patients with large granular leukemia consist of cytotoxic effector T cells expressing the activating CD94:NKG2C/E and NKD2D killer cell receptors	Blood			2003	210	144

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Hoffmann, Till Peter Joseph