T Regulator Cells (Treg) In Patients with Myelofibrosis

Abstract

5051 Primary myelofibrosis (PMF) and myelofibrosis post essential thrombocytosis (MF-ET) or myelofibrosis post polycythemia vera (MF-PV) have been reported to be associated with autoimmune phenomenon, such as Coomb positive anemia, lupus anticoagulant, positive ANA and the presence of circulating immune complex etc. Regulatory T cells (Treg) also have known to play important roles in modulating immune responses. Therefore we studied Treg cells in 25 patients with MF including PMF (12), MF-ET (8), MF-PV (5) and compared with other MPD including ET (7), PV (8), and normal volunteer controls (17). Mononuclear cells (MNC) were separated from peripheral blood. 106 MNCs were stained for flow cytometry analysis using Treg Detection Kit from Miltenyi Biotec Inc (Auburn, CA). The numbers of Treg was calculated as the percentage of positive CD4+ CD25+ FoxP3+ T cells (Treg) from the numbers of gated CD4+ cells. Treg function was evaluated by XTT cell proliferation assay (Invitrogen) with ratios of Treg vs. T-effector cells (CD4+ CD25-) at 1:1, 1:2, 1:4, and 0:1 in the presence of anti-CD3 CD28 microbeads (Invitrogen). The results (mean ± SE) showed numbers of Treg cells in MF were 0.73 + 0.08, other MPD were 1.37 ± 0.22, and normal controls were 0.96 ± 0.27 (p=NS). Treg function was evaluated in 12 patients with MF and 6 normal volunteer controls. Four MF patients were found to have significant lower values than controls. We concluded that in MF, quantitatively Treg were not different from other MPD or normal controls but Treg dysfunction was observed in 30–40 % of MF patients. This could explain why some patients with MF are prone to develop autoimmune phenomenon. Further studies with more patients are in progress. Disclosures: No relevant conflicts of interest to declare.

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms

“…Riley et al showed lower numbers of natural killer (NK) cells in the peripheral blood of MPN patients compared to healthy donors [47]. Regarding the number of regulatory T-cells (Treg) in MPN patients, data are conflicting, as two studies did not demonstrate any difference in peripheral blood Treg levels between MPN patients and healthy controls [48,49], whereas another study showed that patients with MPN have lower numbers of circulating Treg, and this difference was applicable for patients with ET, PV and PMF compared to healthy controls [50]. Two studies have investigated the number of myeloid-derived suppressor cells (MDSC) in the peripheral blood of MPN patients.…”

“…Fewer effector T cells in peripheral blood PMF [40] Fewer NK cells in peripheral blood All MPN [43] Elevated numbers of MDSC in peripheral blood All MPN [47,48] Higher inhibitory potential of MDSC in peripheral blood All MPN [47] Elevated TGFβ production by bone-marrow-derived monocytes PMF [57] Lower levels of naïve T-cells and higher levels of terminally differentiated effector T-cells PV [58] Lower levels HLA-I on monocytes PV [58] Lower levels of HLA-I on mutant cells CALR-mutant MPN [72] Deregulation of genes related to antigen processing and activation as well as immune cell activation and inflammation All MPN [59][60][61] Lower number of myeloid dendritic cells and lower priming potential of myeloid dendritic cells Myeloid cells such as monocytes and myeloid-derived suppressor cells secrete TGF-β and ARG1, respectively. These proteins are highly immunosuppressive to T cells and thus induce immune suppression in the tumor microenvironment (TME).…”

Retracing a Historical Waterway and its Impact on the Community Life of Tangail City, Bangladesh

“…Tangail is the district's principal city. The Tangail municipality, established in 1887 during the British era, has no waste management system (Mirza Shakil, 2022). The canal was the main drainage system for the city.…”