title: Allogeneic lymphocytes exerted graft-versus-host rather than tolerogenic effects on preimmune fetuses.
abstract: BACKGROUND
  Among cell suspensions from different origins, lymphocytes were reported to have the superiority of tolerance-conferring capacity in preimmune hosts. However, this belief was derived directly from murine combinations with fewer major histocompatibility complex (MHC) barriers that are exceptional in the clinical arena. Because of the potential for prenatal tolerance induction to facilitate postnatal therapies, it is important to examine the relative merits and hazards of fully MHC-mismatched naïve lymphocytes as the prenatal tolerogenic agent in the preimmune fetus to cross MHC barriers.
  
  
  METHODS
  In utero injection of C57BL/6 splenic lymphocytes was conducted in gestational day 14 FVB/N fetuses. Then, FVB/N recipients were subjected to the evaluation of hematopoietic chimerism, donor-specific tolerance, and graft-versus-host disease (GVHD).
  
  
  RESULTS
  With a dose of ≥ 5 × 10(5) C57BL/6 lymphocytes, the recipients born alive either died unexpectedly by maternal cannibalization or succumbed to GVHD within postnatal 1 mo. GVHD mice showed significant hematopoietic chimerism that was dominated by donor CD3 T cells. It was found that allogeneic lymphocytes could rapidly damage the fetal liver within 5 d after injection. Fetal recipients could survive a dose of ≤ 2 × 10(5) allogeneic lymphocytes beyond 1 mo of age, but at best showed microchimerism that was insufficient to confer donor-specific skin tolerance.
  
  
  CONCLUSIONS
  Fully MHC-mismatched lymphocytes injected in utero had lethal graft-versus-host effects, which might rapidly develop within 1 wk after injection in preimmune fetuses. They were incapable of conferring significant hematopoietic chimerism and graft tolerance even at bearable doses.
authors.affiliation: Department of Pediatric Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. bx9619@cgmh.org.tw
authors.forename: Jeng-Chang
authors.initials: JC
authors.lastname: Chen
authors.forename: Liang-Shiou
authors.initials: LS
authors.lastname: Ou
authors.forename: Hsiu-Yueh
authors.initials: HY
authors.lastname: Yu
authors.forename: Hsueh-Ling
authors.initials: HL
authors.lastname: Chang
authors.forename: Pei-Yeh
authors.initials: PY
authors.lastname: Chang
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Kuo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D046528:Chimerism; D005260:Female; D005333:Fetus / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D007107:Immune System / Q000196:embryology*; D007108:Immune Tolerance; D017710:Lymphocyte Transfusion; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D016038:Skin Transplantation; D014184:Transplantation, Homologous