Pretransplant identification of acute rejection risk following kidney transplantation

Lack of an accepted definition for 'high immunological risk' hampers individualization of immunosuppressive therapy after kidney transplantation. For recipient-related risk factors for acute rejection, the most compelling evidence points to younger age and African American ethnicity. Recipient gender, body mass, previous transplantation, and concomitant infection or disease do not appear to be influential. Deceased donation now has only a minor effect on rejection risk, but older donor age remains a significant predictor. Conventional immunological markers (human leukocyte antigen [HLA] mismatching, pretransplant anti-HLA alloantibodies, and panel reactive antibodies) are being reassessed in light of growing understanding about the role of donor-specific antibodies (DSA). At the time of transplant, delayed graft function is one of the most clear-cut risk factors for acute rejection. Extended cold ischemia time (≥24 h) may also play a contributory role. While it is not yet possible to establish conclusively the relative contribution of different risk factors for acute rejection after kidney transplantation, the available data point to variables that should be taken into account at the time of transplant. Together, these offer a realistic basis for planning an appropriate immunosuppression regimen in individual patients

Unexpected impairment of TNF-α-induced maturation of human dendritic cells in vitro by IL-4

International audienceBackground: An efficient strategy for programing dendritic cells (DCs) for cancer immunotherapy is the optimiza‑ tion of their maturation so that they can efficiently stimulate cancer‑specific T cell responses. Interleukin (IL)‑4 has appeared as an essential cytokine, widely used in vitro with granulocyte macrophage‑colony stimulating factor (GM‑CSF) to differentiate monocytes into immature DCs (iDC) and to prevent macrophage formation. Conflicting data have been published regarding the effect of IL‑4 on functional DC maturation. To further understand IL‑4's effects on DC maturation and function in vitro, we choose the most commonly used maturation factor tumor necrosis factor (TNF)‑α. Methods: Human monocyte‑derived iDC were treated for 48 h with GM‑CSF and TNF‑α in the presence (IL‑4 + ‑DC) or absence (IL‑4 − ‑DC) of IL‑4 and functions of both DC populations were compared. Results: On mixed lymphocyte reaction assay, IL‑4 + ‑DC were less potent than IL‑4 − ‑DC at inducing the proliferation of allogeneic CD4 + T cells and the proportion of activated T cells expressing CD69 and/or CD25 was smaller. Interleu‑ kin‑4 reduced the cell‑surface expression of TNF‑α‑induced DC maturation markers CD83, CD86, HLA‑DR and CD25 and generated a heterogeneous population of DCs. IL‑4 + ‑DC secreted less IL‑12 and more IL‑10 than IL‑4 − ‑DC follow‑ ing activation by soluble CD40L, and IL‑4 + ‑DC‑activated T cells secreted lesser amounts of T helper (Th) 1 cytokines (IL‑2 and interferon‑γ). Importantly, IL‑4 impaired the in vitro migratory capacity of DCs in response to CCL21 and CCL19 chemokines. This effect was related to reduced expression of CCR7 at both mRNA and protein levels. Conclusion: Interleukin‑4 used with GM‑CSF and TNF‑α during the maturation of DCs in vitro impaired DC functions and disturbed the maturation effect of TNF‑α. Finally, our study reinforces the view that the quality of the DC matura‑ tion stimulus, which regulates DC migration and cytokine production, may be a decisive feature of the immunogenic‑ ity of DCs

Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

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