title: Transplantation tolerance to a single noninherited MHC class I maternal alloantigen studied in a TCR-transgenic mouse model.
abstract: The mechanisms underlying tolerance to noninherited maternal Ags (NIMA) are not fully understood. In this study, we designed a double-transgenic model in which all the offspring's CD8(+) T cells corresponded to a single clone recognizing the K(b) MHC class I protein. In contrast, the mother and the father of the offspring differed by the expression of a single Ag, K(b), that served as NIMA. We investigated the influence of NIMA exposure on the offspring thymic T cell selection during ontogeny and on its peripheral T cell response during adulthood. We observed that anti-K(b) thymocytes were exposed to NIMA and became activated during fetal life but were not deleted. Strikingly, adult mice exposed to NIMA accepted permanently K(b+) heart allografts despite the presence of normal levels of anti-K(b) TCR transgenic T cells. Transplant tolerance was associated with a lack of a proinflammatory alloreactive T cell response and an activation/expansion of T cells producing IL-4 and IL-10. In addition, we observed that tolerance to NIMA K(b) was abrogated via depletion of CD4(+) but not CD8(+) T cells and could be transferred to naive nonexposed mice via adoptive transfer of CD4(+)CD25(high) T cell expressing Foxp3 isolated from NIMA mice.
authors.affiliation: Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Stéphane M
authors.initials: SM
authors.lastname: Caucheteux
authors.forename: Cécile
authors.initials: C
authors.lastname: Vernochet
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tanaka
authors.forename: Colette
authors.initials: C
authors.lastname: Kanellopoulos-Langevin
authors.forename: Gilles
authors.initials: G
authors.lastname: Benichou
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D008431:Maternal-Fetal Exchange / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D018448:Models, Immunological; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D023001:Transplantation Tolerance / Q000235:genetics*
chemical_list: D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D011948:Receptors, Antigen, T-Cell