Lima Margarida, Almeida Julia, Dos Anjos Teixeira Maria, Alguero Md Maria del Carmen, Santos Ana Helena, Balanzategui Ana, Queirós Maria Luís, Bárcena Paloma, Izarra Antonio, Fonseca Sónia, Bueno Clara, Justiça Benvindo, Gonzalez Marcos, San Miguel Jesús F, Orfao Alberto
Serviço de Hematologia Clinica, Unidade de Citometria, Hospital Geral de Santo Antonio, Porto, Portugal.
Am J Pathol. 2003 Aug;163(2):763-71. doi: 10.1016/s0002-9440(10)63703-0.
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.
大颗粒淋巴细胞（LGL）白血病是一种公认的成熟T-CD8(+)疾病，自然杀伤细胞疾病较少见；相比之下，CD4(+) T-LGL的单克隆扩增在文献中仅有零星报道。在本文中，我们在56个月的时间里，对220万居民群体中CD4(+) T-LGL单克隆扩增的发生率进行了研究，并分析了34例连续病例的克隆性CD4(+) T细胞的免疫表型和细胞因子产生模式。与CD8(+) T-LGL白血病一样，CD4(+) T-LGL白血病患者病情进展缓慢；然而，与CD8(+) T-LGL白血病不同的是，他们没有血细胞减少和自身免疫现象，且常伴有肿瘤形成，这通常决定了疾病的临床进程。单克隆CD4(+) T-LGL表现为TCRαβ表达、不同水平的CD8（CD8(-/+dim)）以及均一的典型细胞毒性（颗粒酶B(+)、CD56(+)、CD57(+)、CD11b(+/-)）和活化/记忆T细胞（CD2(+bright)、CD7(-/+dim)、CD11a(+bright)、CD28(-)、CD62L(-) HLA-DR(+)）免疫表型。此外，它们表现出Th1型细胞因子产生模式[γ干扰素(++)、肿瘤坏死因子-α(++)、白细胞介素（IL-2）(-/+)、IL-4(-)、IL-10(-)、IL-13(-)]。TCR-Vβ库的表型分析显示TCR-Vβ单克隆大量扩增；在分析的34例病例中，仅有有限数量的TCR-Vβ家族有表现。这些发现表明，单克隆TCRαβ(+)/CD4(+)/NKa(+)/CD8(-/+dim) T-LGL代表了一种不同于CD8(+) T-LGL和自然杀伤细胞型LGL白血病的单克隆LGL淋巴增殖性疾病亚组。需要更长的随访时间来确定这种克隆性疾病的确切意义。
