Type I and Type II T Cell Profiles in Chronic Myelogenous Leukemia

Tsuda, Hiroyuki; Yamasaki, Hiroshi

doi:10.1159/000041027

Cited by 10 publications

(8 citation statements)

References 9 publications

(8 reference statements)

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“…IM inhibits activation and proliferation of CD4 T lymphocytes in vitro, suppresses CD4 T cell cytokine secretion, and modulates a shift toward a Th2 response (15,19,74). In addition, because IM influences Ag-presenting functions of dendritic cells, the effect of IM on APCs may compromise CD4 Th activity as well as have a direct effect on CD8 T cell function (10,75,76).…”

Section: Discussionmentioning

confidence: 99%

Imatinib Mesylate Inhibits Antigen-Specific Memory CD8 T Cell Responses In Vivo

Sinai

Berg

Haynie

et al. 2007

The Journal of Immunology

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Imatinib mesylate (IM) is effective at inducing complete cytogenetic remission in patients with chronic myelogenous leukemia. Because its influence on CD8 T cell responsiveness in vivo is unknown, we investigated the effects of IM by analyzing the response of OT-1 CD8 T cells to Listeria monocytogenes (LM) that express the cognate epitope OVA257–264 (LM-OVA). In vitro, IM had no effect on Ag-specific expansion, cell division, cell cycle progression, or IFN-γ expression in naive or memory OT-1 T cells. However, IM induced apoptosis of naive and memory OT-1 T cells at doses of >5 μM. At 15 μM IM, OT-1 T cells did not survive in in vitro cultures. The primary response of OT-1 T cells in vivo to LM-OVA infection was unaltered. In contrast, continuous IM treatment resulted in a diminished memory OT-1 response. The expression of IL-7Rα, a receptor required for memory cell survival, was lower (on OT-1 cells) in animals receiving IM. These results indicate that IM treatment affects the ability of the CD8 memory pool to respond to Ag and has the potential to increase susceptibility to infection.

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Section: Discussionmentioning

confidence: 99%

Imatinib Mesylate Inhibits Antigen-Specific Memory CD8 T Cell Responses In Vivo

Sinai

Berg

Haynie

et al. 2007

The Journal of Immunology

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“…Cell number and cytokine secretion in AML N Panoskaltsis et al (CML), 17,18,28 studies in AML have been lacking. The extent and type of cytokine activity shown in the present work in patients with untreated AML were unexpected (Figures 5 and 6).…”

Section: Discussionmentioning

confidence: 99%

Quantification and cytokine production of circulating lymphoid and myeloid cells in acute myelogenous leukaemia

2003

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A simple assay was developed to assess the potential of patients with acute myelogenous leukaemia (AML) to respond to immunotherapy. Lymphocytes, monocytes and leukaemic blasts with their corresponding intracellular cytokine profiles were evaluated by four-colour flow cytometry. In 50 ll samples of whole blood, surface labelling for CD45, CD8 and CD3 was used for cell identification prior to intracellular staining for interleukin (IL)-4, IL-10, IL-12 and interferon (IFN)-c. Absolute numbers of CD8 + and CD8 À (putative CD4 + ) T-cells, NK cells (CD8 + /CD3 À ) and monocytes were determined by reference to a fixed number of added fluorescent beads. The absolute numbers of CD8 À and CD8 + T-cells in the blood of patients with AML were similar to those of normal controls. More of the lymphocytes in the blood of leukaemic patients spontaneously produced cytokines compared with those of controls. Furthermore, primary AML blasts secreted predominantly IFN-c. After recovery from chemotherapy, lymphocyte counts tended to be lower than in normals and reduction of NK cells reached significance after the second chemotherapy (P ¼ 0.01). A prominent CD8 lo /CD3 lo-int lymphocyte subset appeared after recovery in some patients. This laboratory application of the study of cell subsets and intracellular cytokines in patients undergoing treatment may be helpful in monitoring immunological responses in AML.

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“…The phenotypic and functional abnormalities of the immune system of CML patients have been well described (Spiers et al , 1977; Dowding et al , 1984; Tsuda & Yamasaki, 2000). Several reports have suggested that NK cells decrease in number and function during the course of CML, and are restored in accordance with a reduction in white blood cell counts (Pierson & Miller, 1996; Guarini et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Extensive examination of the T‐cell compartments in CML patients has shown increased T‐cell numbers before treatment (Spiers et al , 1977) due to balanced expansion of helper and suppressor cells (Dowding et al , 1984), or increased anergic T lymphocytes (Tsuda & Yamasaki, 2000). In contrast, a marked decline in CD8 lymphocytes, compared with CD4 lymphocytes, has been reported at diagnosis but not at the stage of complete remission (Guarini et al, 2001).…”

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confidence: 99%

The naive T‐lymphocyte compartment is well preserved in patients with chronic myelogenous leukaemia in chronic phase

Isoda

Yokohama²,

Maekawa³

et al. 2002

Br J Haematol

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Summary. In chronic myelogenous leukaemia (CML), clonal change occurs in all myeloid and B‐cell lineages, but very rarely T‐cell lineages. A detailed three‐colour cytometric analysis of peripheral lymphocytes was performed in 22 patients with chronic‐phase CML (CP‐CML). CD45 gating analysis was used to discriminate between lymphocytes and basophils. The peripheral lymphocyte pool was comprised of a significant proportion of naive CD4 cells, defined by a CD4+45RA+ phenotype [47·0 ± 19·6% (mean ± SD) of the total CD4+ cells], and naive CD8 cells, defined by a CD8+CD45RA+CD28+ phenotype (35·1 ± 19·7% of total CD8+ cells), even in patients with long disease duration. The percentage of CD8 naive T cells showed inverse correlation with age, whereas no correlation was observed with disease duration. Possible explanations for the preservation of naive lymphocytes include (1) that the naive T cells differentiated from co‐existing normal stem cells or (2) that long‐lived naive T cells persisted from the CML onset and expanded peripherally (thymus independent). Either mechanism or a combination of both mechanisms might contribute to maintaining the naive compartment size.

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Type I and Type II T Cell Profiles in Chronic Myelogenous Leukemia

Cited by 10 publications

References 9 publications

Imatinib Mesylate Inhibits Antigen-Specific Memory CD8 T Cell Responses In Vivo

Imatinib Mesylate Inhibits Antigen-Specific Memory CD8 T Cell Responses In Vivo

Quantification and cytokine production of circulating lymphoid and myeloid cells in acute myelogenous leukaemia

The naive T‐lymphocyte compartment is well preserved in patients with chronic myelogenous leukaemia in chronic phase

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