title: Mixed chimerism and transplant tolerance are not effectively induced in C3a-deficient mice.
abstract: Mixed chimerism, a phenomenon involved in the development of specific alloantigen tolerance, could be achieved through the transplantation of hematopoietic stem cells into properly prepared recipients. Because the C3a complement component modulates hematopoietic cell trafficking after transplantation, in the present study, we investigated the influence of the C3a deficiency on mixed chimerism and alloantigen tolerance induction. To induce mixed chimerism, C57BL/6J (wild-type strain; H-2K(b); I-E(-)) and B6.129S4-C3(tm1Crr)/J (C3a-deficient) mice were exposed to 3 G total body irradiation (day -1). Subsequently, these mice were treated with CD8-blocking (day -2) and CD40L-blocking (days 0 and 4) antibodies, followed by transplantation with 20 × 10(6) Balb/c (H-2K(d); I-E(+)) bone marrow cells (day 0). The degree of mixed chimerism in peripheral blood leukocytes was measured several times during the 20-week experiment. The tolerance to Balb/c mouse antigens was assessed based on the number of lymphocytes expressing Vβ5 and Vβ11 T-cell receptor and on skin-graft (day 0) acceptance. Applying our experimental model, mixed chimerism and alloantigen tolerance were effectively induced in C57BL/6J (wild-type) mice, but not in C3a(-/-) animals. The present study is, to our knowledge, the first to demonstrate that C3a is vital for achieving stable mixed chimerism and related to this induction of transplant tolerance.
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland. Electronic address: poziomka@pum.edu.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Baśkiewicz-Hałasa
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Rogińska
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Piecyk
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Hałasa
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Lejkowska
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Pius-Sadowska
authors.affiliation: Department of General Pathology, Pomeranian Medical University, Szczecin, Poland. Electronic address: machalin@pum.edu.pl.
authors.forename: Bogusław
authors.initials: B
authors.lastname: Machaliński
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D046528:Chimerism; D015926:Complement C3a / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006085:Graft Survival; D006183:H-2 Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016038:Skin Transplantation; D013047:Specific Pathogen-Free Organisms; D018183:Transplantation Chimera; D023001:Transplantation Tolerance / Q000235:genetics / Q000276:immunology*
chemical_list: D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015926:Complement C3a