Allotransplantation

  • Article
    | Open Access

    Donor-specific antibodies in sensitized recipients may cause kidney transplant rejection. Here the authors show that complement component C3 inhibition prolongs graft survival by inhibiting T and B cell proliferation/activation and hence tissue injury, despite antibody levels remaining unaffected.

    • Robin Schmitz
    • , Zachary W. Fitch
    •  & Stuart J. Knechtle
  • Article
    | Open Access

    In hematopoietic stem cell transplants, T cells mediate graft-versus-leukemia (GVL), but GVL can fail leading to leukemia relapse. Here the authors use a mouse model in which T cells target the minor histocompatibility antigen H60 to show how this can occur, characterize the CD8+ T cell response and demonstrate how anti-CD40 antibody therapy improves GVL.

    • Meng Zhou
    • , Faruk Sacirbegovic
    •  & Warren D. Shlomchik
  • Article
    | Open Access

    An increasing number of inflammatory pathologies is associated with IL-1 production downstream of caspases 1 and 11. Here the authors show that graft-versus-host-disease (GvHD) is diminished in mice with genetic or pharmacological ablation of caspase-11, and provide mechanistic insights into the signals leading to caspase-11 activation in GvHD.

    • Yanyan Lu
    • , Ran Meng
    •  & Ben Lu
  • Article
    | Open Access

    Injection of donor apoptotic cells induces graft tolerance in mice. Here the authors combine this approach with short immunosuppressive therapy to achieve long-term tolerance to allogeneic islets and restoration of normoglycemia in diabetic nonhuman primates, and delineate cellular and molecular correlates of tolerance induction.

    • Amar Singh
    • , Sabarinathan Ramachandran
    •  & Bernhard J. Hering
  • Article
    | Open Access

    Allogeneic hematopoietic cell transplantation is the standard treatment of acute myeloid leukemia, but many patients relapse. Here the authors show increased markers of exhaustion and cancer antigen specificity within bone marrow-residing memory T cells precede and potentially predict the relapse.

    • Maddalena Noviello
    • , Francesco Manfredi
    •  & Chiara Bonini
  • Article
    | Open Access

    Allograft can induces local chronic inflammation, but how this feeds back to regulating late immunity is still not clear. Here the authors show, by charactering B cell transcriptome landscape dynamic in human allografts and in mouse kidneys transitioning from acute to chronic injury, that late B cell activation is associated with renal dysfunction and inflammation.

    • Pietro E. Cippà
    • , Jing Liu
    •  & Andrew P. McMahon
  • Article
    | Open Access

    Anti-human leukocyte antigen (HLA) antibodies are important mediators of alloresponses, but structural insights on antibody:HLA interaction are still lacking. Here the authors provide a 2.4 Å structure of antibody:HLA complex, and also analyse HLA features important for other HLA-interacting molecules, to enhance our understanding of alloimmunity.

    • Yue Gu
    • , Yee Hwa Wong
    •  & Paul A. MacAry
  • Article
    | Open Access

    Transplantation of allogeneic bone marrow helps establish chimerism that may induce tolerance to tissue grafts. Here the authors show that a CD117-antibody-drug-conjugate helps precondition the recipients for inducing mixed chimerism and allo-tolerance without clear adverse effects or the need for chronic immune suppression.

    • Zhanzhuo Li
    • , Agnieszka Czechowicz
    •  & Philip M. Murphy
  • Article
    | Open Access

    Allogeneic hematopoietic cell transplantation (allo-HCT) has led to the cure of HIV in one individual, but the underlying mechanisms are unclear. Here, the authors present a model of allo-HCT in SHIV-infected nonhuman primates and show that the SHIV reservoir persists in multiple tissues early after transplantation.

    • Lucrezia Colonna
    • , Christopher W. Peterson
    •  & Leslie S. Kean
  • Article
    | Open Access

    Regulatory macrophages (Mreg) can directly suppress T effector cell responses. Here the authors show that human Mreg also elicit TIGIT+ regulatory T cells by integrating multiple differentiation signals, and that donor Mreg-induced recipient Tregs may promote kidney transplant acceptance in patients.

    • Paloma Riquelme
    • , Jan Haarer
    •  & James A. Hutchinson
  • Article
    | Open Access

    Gut-homing and colonization of T cells are important for maintaining local immune homoeostasis and protective immunity. Here the authors show that the kinase activity of TRPM7 regulates Th17 differentiation and T cell alloreactivity in the gut by modulating SMAD2 activation and CD103 expression in T cells

    • Andrea Romagnani
    • , Valentina Vettore
    •  & Susanna Zierler
  • Article
    | Open Access

    Rhesus macaques are not ideal for studying response to allogeneic hematopoietic stem cell transplant (allo-HSCT) owing to complex MHC genetics that prevent full MHC-matching. Here the authors show that inbred Mauritian-origin cynomolgus macaques are a superior preclinical model of allogeneic stem cell transplantation that mimics diverse clinical outcomes of human allo-HSCT.

    • Benjamin J. Burwitz
    • , Helen L. Wu
    •  & Jonah B. Sacha
  • Article
    | Open Access

    Chronic graft-versus-host disease (cGVHD) is mediated by specific CD4 and B cells, but the relative contribution of extrafollicular and germinal centre (GC) T-B interaction is unclear. Here the authors show that the extrafollicular expansion of a specific CD4 T subset is sufficient for inducing cGVHD while GC is dispensable.

    • Ruishu Deng
    • , Christian Hurtz
    •  & Defu Zeng
  • Article
    | Open Access

    Phosphatidylinositol-3-kinases (PI3K) γ and δ are key regulators of T cell signaling. Here the author show, using mouse heart allograft transplantation models, that PI3Kγ or PI3Kδ deficiency prolongs graft survival, but selective inhibition of PI3Kγ or PI3Kδ reveals alternative transplant survival outcomes post CTLA4-Ig treatment.

    • Mayuko Uehara
    • , Martina M. McGrath
    •  & Reza Abdi
  • Article
    | Open Access

    Major histocompatibility complex (MHC) matching improves graft survival rates after organ transplantation. Here the authors show that in macaques, MHC-matched iPSC-derived neurons provide better engraftment in the brain, with a lower immune response and higher survival of the transplanted neurons.

    • Asuka Morizane
    • , Tetsuhiro Kikuchi
    •  & Jun Takahashi
  • Article
    | Open Access

    Graft-vs.-host disease is a complication of allogenic hematopoietic stem cell transplantation, and is associated with endothelial dysfunction. Here the authors show that activated protein C signals via PAR2/PAR3 to expand Treg cells, mitigating the disease in mice.

    • Satish Ranjan
    • , Alexander Goihl
    •  & Berend Isermann