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Host MHC class II+ antigen-presenting cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions.

ABSTRACT: Following bone marrow transplantation, delayed donor leukocyte infusions (DLIs) can induce graft-versus-leukemia (GVL) effects without graft-versus-host disease (GVHD). These antitumor responses are maximized by the presence of host hematopoietic antigen-presenting cells (APCs) at the time of DLI. Using a tumor-protection model, we demonstrate here that GVL activity following administration of DLIs to established mixed chimeras is dependent primarily on reactivity to allogeneic MHC antigens rather than minor histocompatibility or tumor-associated antigens. CD8(+) T-cell-dependent GVL responses against an MHC class II-negative tumor following delayed DLI require CD4(+) T-cell help and are reduced significantly when host APCs lack MHC class II expression. CD4(+) T cells primed by host APCs were required for maximal expansion of graft-versus-host reactive CD8(+) T cells but not their synthesis of IFN-gamma. In contrast, the GVL requirement for CD4(+) T-cell help was bypassed almost completely when DLI was administered to freshly irradiated recipients, indicating that the host environment is a major factor influencing the cellular mechanisms of GVL.

SUBMITTER: Chakraverty R

PROVIDER: S-EPMC1895539 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature

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Host MHC class II+ antigen-presenting cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions.

Chakraverty Ronjon R Eom Hyeon-Seok HS Sachs Jessica J Buchli Jennifer J Cotter Pete P Hsu Richard R Zhao Guiling G Sykes Megan M

Blood 20060606 6

Following bone marrow transplantation, delayed donor leukocyte infusions (DLIs) can induce graft-versus-leukemia (GVL) effects without graft-versus-host disease (GVHD). These antitumor responses are maximized by the presence of host hematopoietic antigen-presenting cells (APCs) at the time of DLI. Using a tumor-protection model, we demonstrate here that GVL activity following administration of DLIs to established mixed chimeras is dependent primarily on reactivity to allogeneic MHC antigens rath ...[more]

PMID: 16757687

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Project description:Background and objectivesIncreased donor age is one of the most important risk factors for delayed graft function (DGF), and previous studies suggest that the harmful effect of cold ischemia time is increased in kidneys from older donors. Our aim was to study the association of increased donor age and cold ischemia time with the risk of delayed graft function in a large cohort kidney transplants from the current era.Design, setting, participants, & measurementsThe Scientific Registry of Transplant Recipients was used for this observational, retrospective registry analysis to identify all deceased donor kidney transplantations in the United States between 2010 and September 2018, who were on dialysis pretransplantation (n=90,810). The association of donor age and cold ischemia time with the risk of DGF was analyzed in multivariable models adjusted for recipient characteristics (age, race, sex, diabetes, calculated panel-reactive antibodies, pretransplant dialysis duration) and donor characteristics (cause of death, sex, race, body mass index, creatinine, donation after circulatory death status, history of hypertension, and HLA mismatch).ResultsCold ischemia time and donor age were independently associated with the risk of DGF, but the risk of DGF was not statistically significantly lower in donor age categories between 50 and 64 years, compared with donors ≥65 years. The harmful association of cold ischemia time was not higher in kidneys from older donors in any age category, not even among donation after circulatory death donors. When donor risk was assessed with kidney donor profile index, although a statistically significant interaction with cold ischemia time was found, no practically meaningful increase in cold-ischemia susceptibility of kidneys with a high kidney donor profile index was found.ConclusionsWe were unable to demonstrate an association between donor age and DGF. The association of longer cold ischemia time with the risk of DGF was not magnified in older or more marginal donors.

Dataset Information

Host MHC class II+ antigen-presenting cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions.

Publications

Host MHC class II+ antigen-presenting cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions.

Similar Datasets

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