Müller L, Provenzani C, Faul C, Pawelec G
Tübingen Ageing and Tumour Immunology Group (TATI), Section for Transplantation Immunology, University of Tübingen, Otfried-Müller Str. 10, D-72076 Tübingen, Germany.
Br J Haematol. 2001 Mar;112(3):740-8. doi: 10.1046/j.1365-2141.2001.02596.x.
Defects in immune responses are common in patients with chronic myelogenous leukaemia (CML). However, using dendritic cells (DCs) to promote T-cell immunity in vitro may nonetheless elicit potent specific anti-tumour responses for use in immunotherapy. Here, we show that DCs generated from CML patients had a typical dendritic phenotype and were able to stimulate autologous T cells. Three primed T-cell lines were studied in more detail in one patient. They were stimulated by autologous CML cells, but not by normal non-leukaemic cells from the patient's HLA-identical sibling. This was blocked by HLA-DR-specific, but not HLA-DQ- or HLA-DP-specific antibodies. CML-stimulated cytokine secretion, including interferon-gamma and granulocyte macrophage-colony stimulating factor, suggested a Th1-type phenotype for these sensitized anti-leukaemic T cells. This study therefore shows that cells with a functional dendritic phenotype can be generated from the blood of CML patients and are potent inducers of T-cell responses to tumour cells. This approach allows sensitization of patients' T cells by their own particular tumour without the need to identify the exact leukaemia antigens involved, and may find application in immunotherapy of CML.
慢性粒细胞白血病(CML)患者常出现免疫反应缺陷。然而,在体外利用树突状细胞(DCs)促进T细胞免疫仍可能引发有效的特异性抗肿瘤反应,用于免疫治疗。在此,我们表明,由CML患者产生的DCs具有典型的树突状细胞表型,并且能够刺激自体T细胞。在一名患者中对三条致敏T细胞系进行了更详细的研究。它们受到自体CML细胞的刺激,但未受到来自该患者 HLA 相同同胞的正常非白血病细胞的刺激。这被 HLA-DR 特异性抗体阻断,但未被 HLA-DQ 或 HLA-DP 特异性抗体阻断。CML 刺激细胞因子分泌,包括干扰素-γ 和粒细胞巨噬细胞集落刺激因子,表明这些致敏的抗白血病T细胞具有Th1型表型。因此,本研究表明,具有功能性树突状细胞表型的细胞可从CML患者血液中产生,并且是T细胞对肿瘤细胞反应的有效诱导剂。这种方法无需确定具体涉及的白血病抗原,就能使患者的T细胞被其自身特定肿瘤致敏,可能在CML免疫治疗中得到应用。