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Title

TCRαβ+/CD4+ large granular lymphocytosis: A new clonal T-cell lymphoproliferative disorder

AuthorsLima, Margarida; Almeida, Julia ; Balanzategui, Ana; Bárcena, Paloma; Bueno, Clara; González, Marcos ; San Miguel, Jesús F. ; Orfao, Alberto
Issue Date2003
PublisherAmerican Society for Investigative Pathology
Elsevier
CitationAmerican Journal of Pathology 163(2): 763-771 (2003)
AbstractLarge granular lymphocyte (LGL) leukemia is a well-recognized disease of mature T-CD8+ or less frequently natural killer cells; in contrast, monoclonal expansions of CD4+ T-LGL have only been sporadically reported in the literature. In the present article we have explored throughout a period of 56 months the incidence of monoclonal expansions of CD4+ T-LGL in a population of 2.2 million inhabitants and analyzed the immunophenotype and the pattern of cytokine production of clonal CD4+ T cells of a series of 34 consecutive cases. Like CD8+ T-LGL leukemias, CD4+ T-LGL leukemia patients have an indolent disease; however, in contrast to CD8+ T-LGL leukemias, they do not show cytopenias and autoimmune phenomena and they frequently have associated neoplasias, which is usually determining the clinical course of the disease. Monoclonal CD4+ T-LGL showed expression of TCRαβ, variable levels of CD8 (CD8-/+dim) and a homogeneous typical cytotoxic (granzyme B+, CD56+, CD57+, CD11b+/-) and activated/memory T cell (CD2+bright, CD7-/+dim, CD11a+bright, CD28-, CD62L- HLA-DR+) immunophenotype. In addition, they exhibited a Th1 pattern of cytokine production [interferon-γ++, tumor necrosis factor-α++, interleukin (IL-2)-/+, IL-4-, IL-10-, IL-13-]. Phenotypic analysis of the TCR-Vβ repertoire revealed large monoclonal TCR-Vβ expansions; only a restricted number of TCR-Vβ families were represented in the 34 cases analyzed. These findings suggest that monoclonal TCRαβ+/CD4+/NKa+/CD8-/ +dim T-LGL represent a subgroup of monoclonal LGL lymphoproliferative disorders different from both CD8+ T-LGL and natural killer cell-type LGL leukemias. Longer follow-up periods are necessary to determine the exact significance of this clonal disorder.
URIhttp://hdl.handle.net/10261/63185
Identifiersissn: 0002-9440
e-issn: 1525-2191
Appears in Collections:(IBMCC) Artículos
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