Morphology and function of lymphocytes expanded in granular lymphocyte leukemia

(1)颗粒淋巴细胞的免疫学特征：颗粒淋巴细胞增生性疾病(GLPD)患者外周血中扩增的淋巴细胞分为CD3+T细胞型和CD3-16+NK细胞型。T-GLPD的发病率为%，低于西方国家。T-GLPD中的GL通常缺乏非MHC限制性细胞毒作用，具有ADCC活性，而NK-GLPD中的GL通常同时具有非MHC限制性细胞毒和ADCC细胞毒作用。抗CD3和抗CD8单抗可抑制T-GLPD的ADCC，提示CD3和CD8抗原对T-GLPD的ADCC有调节作用。GL表达IL-2受体(R)β链，GL的增殖是通过这种受体以自分泌和旁分泌的方式介导的。抗IL-2Pβ单抗可抑制GL的增殖。(2)GL的超微结构：当γ-TCR阳性的GL与K562靶细胞混合后，GL进入K562细胞。这种现象被称为“占优”。在α-β-TCR阳性的T细胞或NK细胞中未发现大疱病。(3)从GLPD患者和纯红细胞再生障碍性贫血(PRCA)患者中获得的GL集落分析抑制正常供者来源的CFU-E集落，GL的上清液也抑制集落形成。由于在CFU-E培养系统中加入抗干扰素γ抗体可消除GL介导的CFU-E抑制，因此干扰素-γ和/或相关物质可能是抑制作用的原因。(4)TCR基因分析大多数T-GLPD患者表现出TCR-β和伽马基因的单克隆性重排，而NK-GLPD患者仍处于生殖系构型。

(1) Immunological characteristics of granular lymphocytes (GL).Lymphocytes expanded in the peripheral blood in patients with granular lymphocyte proliferative disorders (GLPD) are divided into CD3+ T-cell type and CD3-16+ NK-cell type. The incidence of T- GLPD is 64%, the number being lower than western countries. GL in T-GLPD usually lack non-MHC- restricted cytotoxicity and possess ADCC, whereas those in NK-GLPD possess both non-MHC-restricted and ADCC cytotoxicity. ADCC of T-GLPD is inhibited by the addition of anti-CD3 and anti-CD8 monoclonal antibodies (mAb), suggesting that CD3 and CD8 antigens regulate ADCC in T-GLPD. GL express IL-2 receptor (R)beta chain al one , and the proliferation of GL is mediated thorough this R in autocrine and paracrine fashion. Anti-IL-2Pbeta mAb inhibits GL proliferation.(2) Ultrastructure of GLWhen gamma delta-TCR-positive GL and K562 target cells are mixed, the GL enter into K562 cells. This phenomenon is called emperipolesis. Emperipolesis is not found in alpha beta-TCR-positive T cells or NK cells. Further characterization of emperipolesis is under investigation using gamma delta- T-cell clones.(3) Colony assayGL obtained from patients with GLPD and pure red-cell aplasia (PRCA) inhibit normal donor-derived CFU-E colonies, and the supernatants of GL also inhibit the colony formation. Since anti-interferon gamma- antibody added in the CFU-E culture system abrogates the GL-mediated CFU-E inhibition, it is likely IFN-gamma and/or related substance may be responsible for the inhibition.(4) Analysis of TCR genesMost patients with T-GLPD exhibit monoclonal rearrangements of TCR-beta and gamma genes, whereas those with NK-GLPD remain in germ-line configuration.