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. 2013 Jun;9(6):1200-4.
doi: 10.4161/hv.24250. Epub 2013 Apr 8.

Anti-leukemia T cells in AML: TNF-α⁺ CD8⁺ T cells may escape detection and possibly reflect a stage of functional impairment

Anne Flörcken  1 , Antje van Lessen, Theis H Terwey, Bernd Dörken, Renate Arnold, Antonio Pezzutto, Jörg Westermann
Affiliations

Anti-leukemia T cells in AML: TNF-α⁺ CD8⁺ T cells may escape detection and possibly reflect a stage of functional impairment

Anne Flörcken et al. Hum Vaccin Immunother. 2013 Jun.

Abstract

Leukemia-associated antigens such as proteinase-3 (PR3) and Wilms' tumor protein-1 (WT-1) are potential targets of T-cell responses, which can be monitored by T-cell assays within vaccination trials and after allogeneic stem cell transplantation (SCT). In chronic myeloid leukemia (CML) an aberrant cytokine profile of antigen-specific T-cells with predominant TNF-α secretion has previously been described. The aim of this study was to investigate whether these TNF-α(+)/IFN-γ(-) CD8(+) T-cells can also be observed in AML patients after SCT. Eight HLA-A2(+) AML patients at different time points after SCT were evaluated for HLA-A2-restricted CD8(+) T-cell responses against PR3, WT-1 and influenza-A using pentamer staining and different cytokine-based T-cell assays. Antigen-specific T-cell immune responses against influenza-A and PR3 were observed in 4/8 patients, WT-1-specific T-cells could be detected in 3/8 patients. Interestingly, four different cytokine secretion profiles of antigen-specific T-cells were detected: (1) IFN-γ(+)/TNF-α(+), (2) IFN-γ(+)/TNF-α(-), (3) TNF-α(+)/IFN-γ(-) and (4) IFN-γ(-)/TNF-α(-). TNF-α(+)/IFN-γ(-) CD8(+) T-cells are an interesting biological phenomenon which can obviously be observed also in AML patients. This finding has important implications for both T-cell biology and monitoring within immunotherapy trials. The functional characterization of these TNF-α(+)/IFN-γ(-) CD8(+) T-cells needs further investigations.

Keywords: AML; IFN-γ; T cell response; TNF-α; cytokine profile.

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Figures

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Figure 1. Intracytoplasmatic cytokine staining (ICS). Intracytoplasmatic cytokine staining (IFN-γ and TNF-α) of CD8+ T cells, after in vitro stimulation with peptide- pulsed PBMC (patient # 8). Control, irrelevant HLA-A2+ peptide.
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Figure 2. Cytometric bead array (CBA) and IFN-γ ELISpot in patients with TNF-α+/ IFN-γ- CD8+ T cells. TNF-α+/ IFN-γ- antigen-specific T cell responses in patients #3 and #8 as measured by CBA and IFN-γ ELISpot. *, peptide-specific cytokine secretion; **, detectable over background, but not meeting our predefined cut-off for specificity. INFL, Influenza-A; IFN-γ, Interferon-γ; PR3, proteinase-3; TNF-α, Tumor necrosis factor-α; WT1, Wilms´ tumor protein- 1.
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