title: High Frequencies of Anti-Host Reactive CD8+ T Cells Ignore Non-Hematopoietic Antigen after Bone Marrow Transplantation in a Murine Model.
abstract: BACKGROUND
  Graft versus host disease (GvHD) occurs in 20% of cases with patients having an MHC I matched bone marrow transplantation (BMT). Mechanisms causing this disease remain to be studied.
  
  
  METHODS
  Here we used a CD8+ T cell transgenic mouse line (P14/CD45.1+) and transgenic DEE mice bearing ubiquitously the glycoprotein 33-41 (GP33) antigen derived from the major lymphocytic choriomeningitis virus (LCMV) epitope to study mechanisms of tolerance in anti-host reactive CD8+ T cells after BMT.
  
  
  RESULTS
  We found that anti-host reactive CD8+ T cells (P14 T cells) were not negatively selected in the thymus and that they were present in wild type (WT) recipient mice as well as in DEE recipient mice. Anti-host reactive CD8+ T cells ignored the GP33 antigen expressed ubiquitously by host cells but they could be activated ex vivo via LCMV-infection. Lipopolysaccharides (LPS) induced transient cell damage in DEE mice bearing anti-host reactive CD8+ T cells after BMT, suggesting that induction of host inflammatory response could break antigen ignorance. Introducing the GP33 antigen into BM cells led to deletion of anti-host reactive CD8+ T cells.
  
  
  CONCLUSIONS
  We found that after BMT anti-host reactive CD8+ T cells ignored host antigen in recipients and that they were only deleted when host antigen was present in hematopoietic cells. Moreover, LPS-induced immune activation contributed to induction of alloreactivity of anti-host reactive CD8+ T cells after BMT.
authors.forename: Asmae
authors.initials: A
authors.lastname: Gassa
authors.forename: Halime
authors.initials: H
authors.lastname: Kalkavan
authors.forename: Fu
authors.initials: F
authors.lastname: Jian
authors.forename: Vikas
authors.initials: V
authors.lastname: Duhan
authors.forename: Vishal
authors.initials: V
authors.lastname: Khairnar
authors.forename: Namir
authors.initials: N
authors.lastname: Shaabani
authors.forename: Nadine
authors.initials: N
authors.lastname: Honke
authors.forename: Alexander
authors.initials: A
authors.lastname: Carpinteiro
authors.forename: Lacramioara
authors.initials: L
authors.lastname: Botezatu
authors.forename: Pietro
authors.initials: P
authors.lastname: Crivello
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dolff
authors.forename: Stanislav
authors.initials: S
authors.lastname: Ferencik
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Cyrus
authors.initials: C
authors.lastname: Khandanpour
authors.forename: Katharina
authors.initials: K
authors.lastname: Fleischhauer
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wahlers
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hardt
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006086:Graft vs Host Disease / Q000209:etiology / Q000378:metabolism; D007108:Immune Tolerance; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D014184:Transplantation, Homologous; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase