title: Asialo GM1 positive CD8+ T cells induce skin allograft rejection in the absence of the secondary lymphoid organs.
abstract: BACKGROUND
  Secondary lymphoid organs are considered to be the only organs in which APCs and naïve T cells interact to initiate adaptive immune responses. Aly/aly mice are autosomal recessive mutants of C57BL/6 mice, and lack lymph nodes and Peyer's patches. In this study, we investigated immune responses to skin allografts in splenectomized aly/aly mice, which lack secondary lymphoid organs completely, and examined the effect of anti-asialo GM1 (AsGM1) antibodies on these responses.
  
  
  METHODS
  Skin allografts were transplanted to 1) heterozygous aly/+ mice, which had normal secondary lymphoid organs, 2) splenectomized aly/+ mice, 3) aly/aly mice, and 4) splenectomized aly/aly mice, with and without anti-AsGM1 antibody treatment. Graft survival time and alloreactive antibody production were investigated.
  
  
  RESULTS
  Heterozygous aly/+ mice and splenectomized aly/+ mice rejected skin allografts acutely. Aly/aly mice also rejected skin allografts, but at a later time than aly/+ mice. Sixty percent of splenectomized aly/aly mice rejected skin allografts within 120 days. Serial administration of anti-AsGM1 antibodies prevented skin allograft rejection in splenectomized aly/aly mice during the same 120-day period of observation. After ceasation of anti-AsGM1 antibody treatment, skin allografts were rejected; we observed a simultaneous increase in AsGM1 expression on CD8+ T cells. Alloreactive antibodies were detected in both splenectomized aly/aly mice that rejected skin allografts and in splenectomized aly/aly mice that accepted skin allografts after treatment with anti-AsGM1 antibodies.
  
  
  CONCLUSIONS
  Cytotoxic and humoral immune responses to skin allografts could be initiated despite the absence of secondary lymphoid organs. AsGM1+ cells were important effector cells in secondary lymphoid organ-independent skin allograft rejection.
authors.affiliation: Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamanokuchi
authors.forename: Iwao
authors.initials: I
authors.lastname: Ikai
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishitai
authors.forename: Takakazu
authors.initials: T
authors.lastname: Matsushita
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sugimoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Shiotani
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamaoka
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D005677:G(M1) Ganglioside / Q000032:analysis*; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D007518:Isoantibodies / Q000096:biosynthesis; D008198:Lymph Nodes / Q000002:abnormalities; D008221:Lymphoid Tissue / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D010581:Peyer's Patches / Q000002:abnormalities; D016038:Skin Transplantation / Q000276:immunology*; D013156:Splenectomy; D013601:T-Lymphocytes / Q000737:chemistry* / Q000502:physiology*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D007518:Isoantibodies; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside