T cells from indolent CLL patients prevent apoptosis of leukemic B cells in vitro and have altered gene expression profile

• Published in: Cancer Immunology, Immunotherapy Vol. 62; no. 1; pp. 51 - 63
• Main Authors: Kiaii, Shahryar, Kokhaei, Parviz, Mozaffari, Fariba, Rossmann, Eva, Pak, Fatemeh, Moshfegh, Ali, Palma, Marzia, Hansson, Lotta, Mashayekhi, Kaveh, Hojjat-Farsangi, Mohammad, Österborg, Anders, Choudhury, Aniruddha, Mellstedt, Håkan
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.01.2013; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Apoptosis; Apoptosis - immunology; B-Lymphocytes - immunology; Cancer; Cancer och onkologi; Cancer Research; Cells; Cloning; Coculture Techniques; Female; Flow Cytometry; Gene expression; Hospitals; Humans; Immunoblotting; Immunologi inom det medicinska området; Immunology; Klinisk medicin; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Lymphocytes; Male; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Medicinska och farmaceutiska grundvetenskaper; Middle Aged; Monoclonal antibodies; Multiple myeloma; Oncology; Original; Original Article; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - immunology; Transcriptome; Sweden; Germany; Gene array; CLL; T cell; Apoptosis
• ISSN: 0340-7004; 1432-0851; 1432-0851
• DOI: 10.1007/s00262-012-1300-y

T cells may have a role in sustaining the leukemic clone in chronic lymphocytic leukemia (CLL). In this study, we have examined the ability of T cells from CLL patients to support the survival of the leukemic B cells in vitro. Additionally, we compared global gene expression of T cells from indolent CLL patients with healthy individuals and multiple myeloma (MM) patients. Apoptosis of purified leukemic B cells was inhibited in vitro when co-cultured with increasing numbers of autologous T cells ( p  < 0.01) but not autologous B and T cells of normal donors. The anti-apoptotic effect exceeded that of the anti-apoptotic cytokine IL-4 ( p  = 0.002) and was greater with CD8+ cells ( p  = 0.02) than with CD4+ cells ( p  = 0.05). The effect was depended mainly on cell–cell contact although a significant effect was also observed in transwell experiments ( p  = 0.05). About 356 genes involved in different cellular pathways were deregulated in T cells of CLL patients compared to healthy individuals and MM patients. The results of gene expression profiling were verified for 6 genes (CCL4, CCL5 (RANTES), XCL1, XCL2, KLF6, and TRAF1) using qRT–PCR and immunoblotting. Our results demonstrate that CLL-derived T cells can prevent apoptosis of leukemic B cells and have altered expression of genes that may facilitate the survival of the leukemic clone.