Open AccessInduction of Alloanergy in Human Donor T Cells Without Loss of Pathogen or Tumor Immunity
Author(s) -
Jeffrey K. Davies,
Dongin Yuk,
Lee M. Nadler,
Eva C. Guinan
Publication year - 2008
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/tp.0b013e3181861b6c
Subject(s) - immunology , cd8 , immune system , antigen , t cell , transplantation , human leukocyte antigen , biology , immunity , flow cytometry , peripheral blood mononuclear cell , cytotoxic t cell , in vitro , medicine , biochemistry
Human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic stem cell transplantation (HSCT) is limited by acute graft-versus-host disease (aGvHD). Nonselective T-cell depletion effectively prevents severe aGvHD but profoundly impairs donor-derived immune reconstitution, increasing infection and disease relapse. The strategy of induction of alloantigen-specific hyporesponsiveness ("alloanergization") in donor bone marrow by allostimulation with costimulatory blockade before haploidentical transplantation has demonstrated early promise in reducing severe aGvHD. However, the differential effect of alloanergization on CD4+ and CD8+ donor T-cell subsets and the degree to which beneficial pathogen- and tumor-immune responses are retained have not been extensively examined.