title: TCRalphabeta+/CD4+ large granular lymphocytosis: a new clonal T-cell lymphoproliferative disorder.
abstract: Large 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-LGLshowed expression of TCRalphabeta, 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-gamma(++), tumor necrosis factor-alpha(++), interleukin (IL-2)(-/+), IL-4(-), IL-10(-), IL-13(-)]. Phenotypic analysis of the TCR-Vbeta repertoire revealed large monoclonal TCR-Vbeta expansions; only a restricted number of TCR-Vbeta families were represented in the 34 cases analyzed. These findings suggest that monoclonal TCRalphabeta(+)/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.
authors.affiliation: Serviço de Hematologia Clinica, Unidade de Citometria, Hospital Geral de Santo Antonio, Porto, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Lima
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Maria
authors.initials: M
authors.lastname: Dos Anjos Teixeira
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Alguero Md
authors.forename: Ana Helena
authors.initials: AH
authors.lastname: Santos
authors.forename: Ana
authors.initials: A
authors.lastname: Balanzategui
authors.forename: Maria Luís
authors.initials: ML
authors.lastname: Queirós
authors.forename: Paloma
authors.initials: P
authors.lastname: Bárcena
authors.forename: Antonio
authors.initials: A
authors.lastname: Izarra
authors.forename: Sónia
authors.initials: S
authors.lastname: Fonseca
authors.forename: Clara
authors.initials: C
authors.lastname: Bueno
authors.forename: Benvindo
authors.initials: B
authors.lastname: Justiça
authors.forename: Marcos
authors.initials: M
authors.lastname: Gonzalez
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D015458:Leukemia, T-Cell / Q000276:immunology* / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology*; D008218:Lymphocytosis / Q000276:immunology* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta