Marx for his times. Book Review of: 'Karl Marx : greatness and illusion' by Gareth Stedman Jones

Potential downstream targets for CD274. RNA-sequencing was performed with WT and CD274-null LICs, and the candidate genes related to proliferation and cell cycle was analyzed. (PDF 116 kb

Clinical characteristics of patients with B-cell NHL.

<p>DLBCL indicates diffuse large B-cell lymphoma; MCL, mantle cell lymphoma; new, a diagnosis of lymphoma with no previous history of lymphoproliferative disease; MZL, marginal zone lymphoma; and SLL, small lymphocytic lymphoma.</p

Elevated frequencies of CD4⁺CD25⁺FoxP3⁺CD127^lo Treg in PB, BM and involved lymphatic tissues in patients with B-cell NHL.

<p>(A) Dot plots were gated on CD4⁺ T cells (based on forward and side scatter and CD4 staining). The number in the dot plot represents the percentage of gated cells expressing the relevant marker. (B) Frequencies of CD4⁺CD25⁺FoxP3⁺CD127^lo Treg in PB, BM and involved lymphatic tissues from patients with B-cell NHL and HVs were quantified using flow cytometric analysis. (C) Frequencies of CD4⁺CD25⁺FoxP3⁺CD127^lo Treg in PB, BM and involved lymphatic tissues from the same patients with B-cell NHL were measured as described earlier. (D) Frequencies of CD4⁺CD25⁺FoxP3⁺CD127^lo Treg in PB, BM and involved lymphatic tissues from indolent B-cell NHL patients and aggressive B-cell NHL patients were measured as described earlier. (E) Frequencies of CD4⁺CD25⁺FoxP3⁺CD127^lo Treg in BM and involved lymphatic tissues from patients with B-cell NHL were measured as described earlier. Each open circle represents a single individual assessed in the respective group and numbers on the left of horizontal bars represent the group means.</p

Functional analysis of induced FoxP3-expressing CD4 cells in vitro.

<p>(A) CD4⁺CD25⁻ cells isolated from a patient with B-cell NHL were co-cultured with purified autologous B cells for 5 days. Then, CD4⁺CD25⁺ T cells were isolated and cocultured with CFSE-labeled CD4⁺CD25⁻ T cells for 4 days in the presence of γ-irradiated (30 Gy) PBMCs, with each population 2×10⁵ cells. Histograms showed the profile of CFSE-labeled CD4⁺CD25⁻ T cells and the proliferated CD4⁺CD25⁻ T cells was measured by the percentage of CFSE^dim cells, as indicated. The converted Treg could inhibit the proliferation of allogeneic CD4⁺CD25⁻ T cells (<i>P</i><0.01). Two BM samples (patients 8 and 11) and one LN sample (patient 24) were tested, and a representative experiment of three was presented. (B) CD4⁺CD25⁻ cells isolated from a HV or patient with B-cell NHL were co-cultured with purified respective autologous B cells for 5 days. Then, the cells were stimulated with PMA plus ionomycin for 5 hours in the presence of BFA. Cells were harvested and costained with anti-CD3 and anti-CD8. Next, cells were fixed, permeabilized and stained with anti-FoxP3, anti-IL-2, anti-IFN-γ, anti-IL-4, or anti-IL-17. Dot plots were gated on CD3⁺CD4⁺(CD3⁺CD8⁻) T cells, and the numbers within each quadrant represent the percentages of CD4⁺ T cells. Two BM samples (patients 8 and 11) and one LN sample (patient 24) were tested, and the results were representatives of three independent experiments.</p

Malignant B cells induce FoxP3 expression and Treg conversion from CD4⁺CD25⁻ T cells, which partly depends on the interaction of between PD-1 and B7-H1.

<p>(A,B) Malignant B cells, but not normal B cells, were able to induce FoxP3 expression in autologous conventional T cells. CD4⁺CD25⁻ T cells were cultured for 5 days with X-ViVO™ 15 medium alone or purified autologous B cells in the presence of 100 IU/ml IL-2. The cells were then harvested, stained, and analyzed for the percentage of CD4⁺FoxP3⁺ cells. The number in the dot plot represents the percentage of gated cells expressing the relevant marker. Each open circle represents a single individual and numbers on the left of horizontal bars represent the group means. The results were representative of seven independent experiments. (C,D) Malignant B cells, but not tumor-infiltrating T cells, were able to induce the conversion of Treg from conventional T cells. CD4⁺CD25⁻ T cells isolated from involved lymphatic tissues of B-cell NHL were co-cultured with normal B cells for 5 days. CD4⁺CD25⁻ T cells isolated from PB of HVs were co-cultured with malignant B cells for 5 days. (E) The expression of B7-H1 was higher in lymphoma B cells than normal B cells. Cells were costained with anti-CD19-FITC and anti-B7-H1-PE, and then were analyzed the expression of B7-H1 on CD19⁺ B cells using flow cytometry. (F,G) Histograms showed the effect of the interaction between PD-1 and B7-H1 on the conversion of Treg from conventional T cells. CD4⁺CD25⁻ T cells were cocultured with autologous B cells purified from patients with B-cell NHL for 5 days. Cells were treated with PD-1 fusion protein or anti-B7-H1 antibody as well as their corresponding controls in the coculture system. A CD4⁺FoxP3⁺ gate was drawn based on their isotype controls. The results were representative of seven independent experiments.</p

Additional file 3: Figure S2. of CD274 promotes cell cycle entry of leukemia-initiating cells through JNK/Cyclin D2 signaling

CD274 is inversely correlated to the overall survival of AML patients. (A) In silico analysis of the expression of CD274 in human AML samples from the curated databases (the HemaExplorer, http://servers.binf.ku.dk/hemaexplorer/ ). (B) In silico analysis of the relationship between CD274 expression level and overall survival in AML patients from the databases of Leukemia Gene Atlas (LGA) ( http://www.leukemia-gene-atlas.org/LGAtlas/ ). (*, p < 0.05). (PDF 176 kb

Additional file 5: Figure S4. of CD274 promotes cell cycle entry of leukemia-initiating cells through JNK/Cyclin D2 signaling

Potential downstream targets for CD274. RNA-sequencing was performed with WT and CD274-null LICs, and the candidate genes related to proliferation and cell cycle was analyzed. (PDF 116 kb