Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion.: Apoptosis and regulatory T cells

International audienceApoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover

Gall bladder: the predominant source of bile IgA in man?

The sedimentation profiles of IgA and Secretory Component (SC) and the concentrations of IgA, IgG, IgM, SC and albumin were evaluated after an overnight fast in gall bladder bile of six adult subjects without hepatobiliary disease. The sedimentation profiles differed from those previously obtained in hepatic bile in three ways: gall bladder bile contained a greater percentage of free-SC, a greater percentage of polymeric-IgA (p-IgA), and a major peak of 14 to 19 S p-IgA associated to SC. In contrast to hepatic bile in which IgG is the predominant Ig, IgA clearly was the predominant Ig in gall-bladder bile, its concentration averaging 92 micrograms/ml. Relative-to-albumin coefficients of excretion of proteins in gall bladder bile averaged 0.99 for IgG, 8.6 for monomeric IgA, 196 for p-IgA and 31 for IgM, indicating that there was a selective excretion of IgA and IgM into gall bladder bile. As compared to hepatic bile, the enrichment of gall bladder bile with IgA and IgM was respectively 6.5 and 11.5 times greater than with IgG. These results suggest that quite a significant amount of p-IgA could have been added to bile during its storage in the gall bladder which should therefore be regarded as the predominant source of bile IgA in humans

Biological Description of 109 Cases of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) from the French Network of BPDCN

WOS:000368021800069International audience55th Annual Meeting and Exposition of the American-Society-of-Hematology - New Orleans, LA 201

Biological Description of 109 Cases of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) from the French Network of BPDCN

WOS:000368021800069International audience55th Annual Meeting and Exposition of the American-Society-of-Hematology - New Orleans, LA 201

How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD3031, CD3041, and cTCL11) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)-like, acute lymphoid leukemia (ALL)-like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])-like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure