title: Antigen-Specific Priming is Dispensable in Depletion of Apoptosis-Sensitive T Cells for GvHD Prophylaxis.
abstract: Prophylactic approaches to graft versus host disease (GvHD) have employed both phenotypic reduction of T cells and selective elimination of host-primed donor T cells in vitro and in vivo. An additional approach to GvHD prophylaxis by functional depletion of apoptosis-sensitive donor T cells without host-specific sensitization ex vivo showed remarkable reduction in GHD incidence and severity. We address the role and significance of antigen-specific sensitization of donor T cells and discuss the mechanisms of functional T cell purging by apoptosis for GvHD prevention. Host-specific sensitization is dispensable because migration is antigen-independent and donor T cell sensitization is mediated by multiple and redundant mechanisms of presentation of major and minor histocompatibility complex and tissue antigens by donor and host antigen-presenting cells. Our data suggest that potential murine and human GvH effectors reside within subsets of preactivated T cells susceptible to negative regulation by apoptosis prior to encounter of and sensitization to specific antigens.
authors.affiliation: Cellect Biomed , Kfar Saba , Israel.
authors.forename: Shai
authors.initials: S
authors.lastname: Yarkoni
authors.affiliation: Bone Marrow Transplant Unit, Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel , Petah Tikva , Israel.
authors.forename: Jerry
authors.initials: J
authors.lastname: Stein
authors.affiliation: Bone Marrow Transplant Unit, Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel , Petah Tikva , Israel.
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.affiliation: Frankel Laboratory, Center for Stem Cell Research, Schneider Children's Medical Center of Israel , Petah Tikva , Israel.
authors.forename: Nadir
authors.initials: N
authors.lastname: Askenasy
keywords: Fas; T cell depletion; TNF receptors; antigen-specific stimulation; apoptosis; graft versus host disease