T cells from indolent CLL patients prevent apoptosis of leukemic B cells in vitro and have altered gene expression profile.
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.
Institute of Cancer, Barts and The London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK.
Shahryar
S
Kiaii
Parviz
P
Kokhaei
Fariba
F
Mozaffari
Eva
E
Rossmann
Fatemeh
F
Pak
Ali
A
Moshfegh
Marzia
M
Palma
Lotta
L
Hansson
Kaveh
K
Mashayekhi
Mohammad
M
Hojjat-Farsangi
Anders
A
Österborg
Aniruddha
A
Choudhury
Håkan
H
Mellstedt
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D059467:Transcriptome