title: T-cell alloreactivity and transplantation outcome: a budding role for heterologous immunity?
abstract: OBJECTIVE
  Despite the association between alloreactive T cells and poor graft survival, the mechanisms behind T-cell-mediated rejection are still under investigation. In this review, we will discuss the latest insights into the impact of T-cell alloreactivity on solid organ transplantation and hematopoietic stem cell transplantation (HSCT), with special emphasis on the potential impact of heterologous immunity.
  
  
  RESULTS
  A large part of the memory T-cell repertoire is induced upon virus infections, and evidence for a role of T-cell receptor cross-reactivity of virus-induced memory T cells against allogeneic human leukocyte antigen (HLA) is accumulating in experimental and clinical solid organ transplantation studies. In HSCT, strong alloreactive potential of naïve T cells causes concerns for graft-versus-host disease while additional HLA-DP matching is suggested to prevent CD4 alloreactivity. Furthermore, virus-induced memory T cells hamper mixed chimerism induction, pointing once more towards a role for heterologous immunity.
  
  
  CONCLUSIONS
  Both memory and naïve T cells contribute to the alloimmune response after transplantation. Monitoring for T-cell phenotypes could help predict rejection episodes and/or graft-versus-host disease, allowing timely intervention. Tailoring donor lymphocyte infusions and additional HLA matching could prevent strong alloreactivity in HSCT. Furthermore, the potential role of heterologous immunity in T-cell alloreactivity and transplantation is gaining interest.
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Heleen
authors.initials: H
authors.lastname: van den Heuvel
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Heidt
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D000818:Animals; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D064789:Immunity, Heterologous; D007156:Immunologic Memory; D016377:Organ Transplantation / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome