Bone marrow-derived T-cell clones obtained from untreated acute myelocytic leukemia exhibit blast directed autologous cytotoxicity

• Published in: Leukemia research 1995-02, Vol.19 (2), p.73-82
• Main Authors: Jahn, Bernhard, Bergmann, Lothar, Weidmann, Eckhart, Brieger, Jürgen, Fenchel, Klaus, Schwulera, Ulrich, Hoelzer, Dieter, Mitrou, Paris Sophokles
• Format: Article
• Language: English
• Subjects: AML; Biological and medical sciences; Bone Marrow Cells; Cells, Cultured; Clone Cells; cytokine secretion; Cytokines - biosynthesis; cytotoxic T-cell clones; Cytotoxicity, Immunologic; Hematologic and hematopoietic diseases; Humans; interleukin 2; Leukemia, Myeloid, Acute - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Receptors, Antigen, T-Cell, alpha-beta - genetics; T-Lymphocytes - immunology
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/0145-2126(94)00119-U

The eradication of minimal residual blast populations by activation of autologous cytotoxic cells with interleukin 2 (IL-2) is a new promising tool in the treatment of acute myelocytic leukemia (AML). However, the immunological effector cells are not yet clearly defined. The present study was designed to investigate the presence of cytotoxic precursor cells in active AML and to identify phenotypical and functional characteristics of autologous anti-leukemic cytotoxic effector cells. For this purpose, mononuclear cells (MNC) containing at least 70% leukemic blasts were isolated from bone marrow of untreated AML and cultured in the presence of 3000 IU/ml recombinant IL-2 (rIL-2) for 6–8 weeks. Under these conditions, T-cells were selected in the bone marrow cultures and overgrew the leukemic blasts. The resulting T-cell populations were cloned by limiting dilution and the clones obtained were characterized for their phenotypical and functional patterns. Totally, cloning resulted in 68 clones and a few cell lines. The clonality was verified by RT PCR analysis of TCR Vβ gene expression. All clones obtained stained positive for CD2, CD3, DR and CD56. The vast majority (68%) of T-cell clones/lines was CD4 +, a few clones expressed CD8 (19%) or CD4 and CD8, and four clones were of TCRγδ origin. Seven of 15 clones tested, including three CD4 +, two CD8 + and two TCRγδ +-clones were found to be cytotoxic against autologous leukemic blast cells. All except one clone expressed oncolytic activities against allogeneic blasts too. One of the TCRγδ +-clones demonstrated NK activity by lysis of K562 targets. The majority of the T-cell-clones released IL-2, IL-8, TNF-α, GM-CSF but only a few IFNγ and expressed high levels of mRNA for IL-2, TGF-β and IL-10. None of the clones was found to produce IL-3, IL-4, IL-7 and TNF-β. The data provide evidence of the existence of T-cell precursors in untreated AML bone marrow differentiating to cytotoxic cells with activity against autologous and allogeneic AML blast cells.