title: Survival of skin allografts is prolonged in mice with a dominant-negative H-Ras.
abstract: Ras is a guanine nucleotide-binding protein that plays a major role in regulating the proliferation of T cells. To investigate the mechanism of the Ras/mitogen-activated protein kinase pathway, one of the downstream signal-transduction pathways of T-cell receptors, in the response to alloantigen, we performed full-thickness skin grafting in the major histocompatibility complex (MHC) incompatible strain BALB/c (H-2Kd) (donor) and T-cell-specific H-Ras dominant-negative (dnRas) transgenic (tg) C57BL/6 (H-2Kb) (recipient) male mice. In vitro and in vivo dnRas tg mouse T-cell proliferation and cytotoxic T lymphocyte (CTL) activity assay were also performed. The median graft survival time in control B6/wild type (wt) mouse allografts was seven days. Conversely, the dnRas tg mouse group exhibited a significant (p<0.01) prolongation of graft survival to 15 days. However, all grafts were eventually rejected after one month. Mixed lymphocyte reaction and popliteal lymph node assay revealed that T-cell proliferation was decreased in response to alloantigen, but CTL activity was not changed in the dnRas tg mice. These results suggested that Ras is essential for peripheral T lymphocytes to respond to allo-MHC antigens, and Ras may be a molecular target for controlling transplant rejection.
authors.affiliation: Laboratory of Transplantation Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Funeshima-Fuji
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujino
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kimura
authors.forename: Shiro
authors.initials: S
authors.lastname: Takahara
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Taichi
authors.initials: T
authors.lastname: Ezaki
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Li
mesh_terms: D000818:Animals; D005799:Genes, Dominant; D011905:Genes, ras; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous; D018631:ras Proteins / Q000235:genetics*
chemical_list: D018631:ras Proteins