Zambello R, Trentin L, Cassatella M A, Raimondi R, Cerutti A, Enthammer C, Facco M, Agostini C, Semenzato G
Padua University School of Medicine, Department of Clinial Medicine, First Medical Clinic, Italy.
Br J Haematol. 1996 Feb;92(2):308-14. doi: 10.1046/j.1365-2141.1996.d01-1495.x.
We investigated the effects of Il-12 on functional properties of CD3+ CD8+ granular lymphocytes (GL) of of patients with lymphoproliferative disease of granular lymphocytes (LDGL). To this aim, in 10 cases with clonal CD3+ GL proliferation (nine cases with an associated TCR alpha/beta receptor and one case with a TCR gamma/delta receptor) we studied the proliferative and cytotoxic activities of resting and alpha CD3 monoclonal antibody (mAb) activated cells in the presence of rIL-12 and anti-IL-12 blocking antibodies. Specific mRNA for IL-12 p40 subunit was also investigated. Our results showed that rIL-12 increased the proliferation of alpha CD3 pre-stimulated GL (2 to 6 times). Further, anti-IL-12 antibodies partially inhibited alpha CD3-induced cell growth, suggesting a role for this cytokine in the alpha CD3-mediated GL activation. The addition of antibodies blocking the p55 and p75 chains of IL-2 receptor (IL-2R) did not inhibit the rIL-12-mediated cell proliferation, indicating that the activity of rIL-12 is dependent of IL-2 in the in vivo expanded GL of patients under study. Concerning the cytotoxic activity, rIL-12 increased the alpha CD3-mediated NK activity against K-562 target cells and alpha CD3 redirected cytotoxicity against P815 target cells. Molecular analysis pointed out that, following alpha CD3 stimulation, patients' GL increased the expression of specific mRNA for the p40 subunit of IL-12 as compared to baseline conditions. Our data indicate that IL-12 is involved in the mechanisms of activation of clonal CD3+ GL in patients with LDGL; these features are consistent with the possibility that this discrete subset of GL might represent in vivo primed cytotoxic T lymphocytes.
我们研究了白细胞介素-12（IL-12）对颗粒淋巴细胞增殖性疾病（LDGL）患者CD3⁺CD8⁺颗粒淋巴细胞（GL）功能特性的影响。为此，在10例克隆性CD3⁺GL增殖患者中（9例伴有TCRα/β受体，1例伴有TCRγ/δ受体），我们研究了在重组人IL-12（rIL-12）和抗IL-12阻断抗体存在的情况下，静息细胞和αCD3单克隆抗体（mAb）激活细胞的增殖和细胞毒性活性。还研究了IL-12 p40亚基的特异性mRNA。我们的结果表明，rIL-12增加了αCD3预刺激的GL的增殖（2至6倍）。此外，抗IL-12抗体部分抑制了αCD3诱导的细胞生长，表明该细胞因子在αCD3介导的GL激活中起作用。添加阻断IL-2受体（IL-2R）p55和p75链的抗体并未抑制rIL-12介导的细胞增殖，表明在本研究的患者体内扩增的GL中，rIL-12的活性不依赖于IL-2。关于细胞毒性活性，rIL-12增加了αCD3介导的针对K-562靶细胞的自然杀伤（NK）活性以及αCD3重定向的针对P815靶细胞的细胞毒性。分子分析指出，与基线条件相比，αCD3刺激后，患者的GL增加了IL-12 p40亚基特异性mRNA的表达。我们的数据表明，IL-12参与了LDGL患者克隆性CD3⁺GL的激活机制；这些特征与这一离散的GL亚群可能代表体内预致敏的细胞毒性T淋巴细胞的可能性一致。
