Cytolytic Pathways Used by Effector Cells Derived from Recipient Naive and Memory T Cells and Natural Killer Cells in Resistance to Allogeneic Hematopoietic Cell Transplantation

During the past decade, 2 major cytolytic pathays used by natural killer (NK) and T cells have been horoughly described. Both the perforin/granzyme nd death receptor (ie, fas/fas ligand [fasL]) pathways ltimately result in apoptosis of the targeted populaion [1]. Studies have been preformed using mutant nd knockout strains to investigate NK and T-cell mpairment in viral and tumor immune responses, as ell as in transplantation models, to investigate the ontribution of these pathways in resistance to allogeeic cell engraftment [2-9]. Several early studies ielded interesting results with regard to cytolytic deciencies and so-called allograft resistance. For examle, major histocompatibility complex (MHC)–hetrozygous recipients were observed to reject donor arental marrow despite granzyme B deficiency [4]. dditionally, lethally conditioned MHC-disparate reipients deficient in perforin or expressing defective asL were also able to reject allogeneic hematopoietic rafts after a standard dose of bone marrow (BM) was ransplanted [2]. By using a different approach in which diphtheria oxin was transgenically expressed under a granzyme B romoter to broadly eliminate cytolytic barrier cell opulations, results were obtained that were similar to hose described previously: no detection was reported f diminution in NK resistance to hematopoietic stem t