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CD8 Suppressor Cells Can Be Induced by Pre-B Acute Lymphoblastic Leukemia As a Potential Mechanism of Immune Escape

Abstract 4797 Suppressor CD8 T-cells have been associated with poor antiviral immunity and, more recently, poor prognosis in hematologic malignancy. We have previously observed that nonprofessional antigen presenting cells, including B-lymphocytes, can induce IL10-secreting CD8 suppressors in the se...

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Bibliographic Details
Published in:Blood 2012-11, Vol.120 (21), p.4797-4797
Main Authors: Shand, Jessica C, Kanu, Alieu, Fry, Terry J
Format: Article
Language:English
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Summary:Abstract 4797 Suppressor CD8 T-cells have been associated with poor antiviral immunity and, more recently, poor prognosis in hematologic malignancy. We have previously observed that nonprofessional antigen presenting cells, including B-lymphocytes, can induce IL10-secreting CD8 suppressors in the setting of lymphopenia. In this study, we hypothesized that pre-B cell acute lymphoblastic leukemia could also induce CD8 suppressors as a potential mechanism of immune escape. To test this hypothesis, naïve murine (B6) CD8 T-cells (CD45.2) specific for the immunodominant HY peptide (HY-CD8), were cultured with a B6 HY-expressing murine pre-B cell acute lymphoblastic leukemia (CD45.2) carrying the human E2A-PBX transgene (E2APBX-ALL). Male B6 CD45.1+ dendritic cells and B-cells served as controls, as did female (HY-) E2APBX-ALL. Production of IFNγ and IL10 was determined by enzyme-linked immunoadsorbent assay (ELISA) at 48–72 hours, and specific identification of IFNγ, IL10 and FoxP3 expression by HY-CD8 was measured by intracellular flow cytometry by gating on live, CD8a+CD45.2+ cells. Surface expression of B7 family costimulatory molecules such as PD1 was also measured. As expected, coculture of activated male dendritic cells (DC) with HY-CD8 generated high levels of IFNγ (1036 pg/ml +/− 40), with 67.2 +/− 9.4% CD8a+CD45.2+IFNγ+ cells at 72 hours. HY-CD8 did not produce detectable IL10 or express FoxP3 by either immunoassay or intracellular stain by 72 hours of culture in the presence of male DC. In contrast, HY-expressing E2APBX ALL induced IL10 production in HY-CD8, significantly less interferon gamma production by immunoassay (576 pg/ml +/− 150, p
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V120.21.4797.4797