Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia

Abstract

Summary. This study analysed a naturally occurring specific cellular immunity against tumour cells in chronic lymphocytic leukaemia (CLL) patients. Five out of eight patients had blood T lymphocytes able to recognize spontaneously and specifically the autologous tumour B cells (proliferation assay). In these five patients, detection of cytokines by realtime reverse transcription polymerase chain reaction (RT-PCR) revealed that granulocyte±macrophage colony-stimulating factor (GM-CSF) was the most abundant cytokine gene expressed by the T cells that recognized the autologous tumour B cells. Other activated cytokine genes were ginterferon (IFN), interleukin (IL)-2 and tumour necrosis factor (TNF)-a, but not IL-4. This profile suggests a type 1 anti-B-CLL T-cell response. CD80 and CD54 were relatively downregulated on the native tumour B cells compared with control normal B cells. Upregulation of CD80 on the leukaemic cells was mandatory for the induction of such a specific T-cell response. CD80 and CD54 monoclonal antibodies inhibited the specific T-cell DNA synthesis proliferation. The proliferative T-cell response was either MHC class I or class II restricted (inhibition by monoclonal antibodies). The specific cytokine gene expression could be found in isolated CD4, as well as CD8, T-cell subsets. This study demonstrated the presence of a potential natural specific CD4, as well as a CD8 type 1 T-cell immunity against the leukaemic CLL tumour B cells in CLL. A further detailed analysis of the spontaneous anti-CLL T-cell immunity is warranted that may facilitate the development of effective anti-tumour vaccines in CLL.

Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy

“…12 Granulocytes were recovered from the top of the erythrocyte layer after Ficoll-Hypaque density-gradient centrifugation. Erythrocytes were lysed by hypo-osmosis in cold water.…”

“…Leukemic B cells and tonsil mononuclear cells were also enriched using nylon wool purification. 12 The purity of isolated mononuclear cells was analyzed by direct immunofluorescence using conjugated monoclonal antibodies (MAb) against CD3, CD19 and CD14 (BD Biosciences, San Jose, CA) and flow cytometry (FACSCalibur BD Biosciences).…”

“…12 T and B lymphocytes were purified from PBMC by negative selection using MACS beads (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany) according to manufacturer's instruction. Leukemic B cells and tonsil mononuclear cells were also enriched using nylon wool purification.…”

Generation of a Dendritic Cell‐based Vaccine in Chronic Lymphocytic Leukaemia Using CliniMACS Platform for Large‐scale Production

“…Our previous studies [9][10][11] as well as those of other investigators [12][13][14] indicate that it is feasible to expand antileukaemic, cytolytic T cells ex vivo. A few target antigens that can be recognized by T cells have also been described in CLL [15].…”

Chronic Lymphocytic Leukemia Cells Bind and Present the Erythrocyte Protein Band 3: Possible Role as Initiators of Autoimmune Hemolytic Anemia

“…In all cases responses were blocked by anti HLA-DR Ab, confirming that the proliferation measured corresponded to CD4 ϩ T cells. It is noteworthy that cultures without Ag showed relatively high [ 3 H]thymidine incorporation (cpm Ͼ1000), which has been shown to be due to T cell responses against the CLL cells themselves (35,36).…”