title: Analysis of tolerance induction using triple chimeric mice: major histocompatibility complex-disparate thymus, hemopoietic cells, and microenvironment.
abstract: BACKGROUND
  Although bone marrow transplantation (BMT) has become a valuable strategy for the treatment of various intractable diseases in recent years, success rates remain low in elderly patients because of low thymic function. We have previously shown that fetal thymus transplantation (TT) with BMT is effective for elderly recipients in mice.
  
  
  METHODS
  We performed fully major histocompatibility complex (MHC)-mismatched fetal TT from B6 (H-2) mice plus allogeneic BMT from C3H/HeN (H-2) mice by intra-bone marrow-BMT (IBM-BMT) using congenitally athymic nude (nu/nu) BALB/c (H-2), or BALB/c adult-thymectomized recipients to obtain triple chimeras. We next carried out the IBM-BMT+TT using senescence-accelerated mouse P1 strain (SAMP1) to examine whether this method would be applicable to aging mice.
  
  
  RESULTS
  Triple chimeric mice survived for a long period with sufficient T-cell functions comparable to the mice treated with BMT plus MHC-matched TT, whereas those without TT survived for a short period with insufficient T-cell reconstitution. Almost all the hematolymphoid cells were derived from donor bone marrow cells. Interestingly, they showed tolerance to all three types of MHC determinants with donor-derived thymic dendritic cells in TT. Triple chimeric SAMP1 also survived for long periods with T-cell functions restored in contrast to non-TT SAMP1 recipients.
  
  
  CONCLUSIONS
  These findings suggest that third party combined TT with allogeneic IBM-BMT may be more advantageous for elderly recipients with low thymic function, than IBM-BMT alone (without TT).
authors.affiliation: Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Cui
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyake
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Kequan
authors.initials: K
authors.lastname: Guo
authors.forename: Yunze
authors.initials: Y
authors.lastname: Cui
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Changye
authors.initials: C
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Takashi
authors.initials: T
authors.lastname: Takaki
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Nishida
authors.forename: Muneo
authors.initials: M
authors.lastname: Inaba
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000375:Aging; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006649:Histocompatibility Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000502:physiology / Q000637:transplantation*; D018183:Transplantation Chimera
chemical_list: D006649:Histocompatibility Antigens