title: Vulnerability of allografts to rejection by MHC class II-restricted T-cell receptor transgenic mice.
abstract: BACKGROUND
  Examination of the in vivo activation and function of CD4+ T cells in response to allografts may advance our understanding of the rejection process. We analyzed the capacity of transgenic class II-restricted CD4 T cells to reject skin, cardiac, and islet transplants.
  
  
  METHODS
  TS1 mice possess a high frequency of CD4+ T cells specific for the immunodominant epitope of the viral hemagglutinin (HA) protein. We analyzed the kinetics of rejection of skin, heart, and islet grafts by naïve and sensitized TS1 mice and by adoptively transferred TS1 lymphocytes.
  
  
  RESULTS
  Rejection of heart transplants was more rapid than skin grafts (mean survival time, 12.9 vs. 26.6 days), and islet grafts survived indefinitely in TS1 mice. These findings may be partly attributable to the supranormal frequency of HA-reactive cells in TS1 mice. In support of this, we found that adoptive transfer of 5 x 10(5) TS1 lymphocytes to Balb/c hosts effected consistent rejection of HA-bearing skin transplants, whereas a significantly greater number (3 x 10(6)) was required for heart transplant rejection. The in vivo proliferative response of HA-specific T cells to heart and skin was found to be robust and predominantly localized to the draining lymph nodes.
  
  
  CONCLUSIONS
  We developed a model of allograft rejection in which the responding T cells and relevant graft antigen are specifically defined. Adoptive transfer of carboxy-fluorescein succinimidyl ester-labeled transgenic T cells allowed us to visualize a robust proliferative response in vivo to heart and skin allografts, which in both cases was localized to regional lymph nodes.
authors.affiliation: Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Major K
authors.initials: MK
authors.lastname: Lee
authors.forename: Xiaolun
authors.initials: X
authors.lastname: Huang
authors.forename: Beth P
authors.initials: BP
authors.lastname: Jarrett
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Moore
authors.forename: Niraj M
authors.initials: NM
authors.lastname: Desai
authors.forename: Moh
authors.initials: M
authors.lastname: Moh Lian
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Markmann
authors.forename: Shaoping
authors.initials: S
authors.lastname: Deng
authors.forename: Adam
authors.initials: A
authors.lastname: Frank
authors.forename: Andrew
authors.initials: A
authors.lastname: Singer
authors.forename: Ergun
authors.initials: E
authors.lastname: Velidedeoglu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Caton
authors.forename: And James F
authors.initials: AJ
authors.lastname: Markmann
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D004198:Disease Susceptibility; D006084:Graft Rejection / Q000209:etiology*; D016027:Heart Transplantation; D006389:Hemagglutinins, Viral / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007156:Immunologic Memory; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000473:pathology / Q000637:transplantation; D014184:Transplantation, Homologous
chemical_list: D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell