title: Inhibition of T cell homing by down-regulation of CD62L and the induction of a Th-2 response as a method to prevent acute allograft rejection in mice.
abstract: OBJECTIVE
  For a successful immune response, migration of lymphocytes to lymphoid organs and other tissues is a key step, as the initial recognition of foreign antigens and activation of lymphocytes takes place in these organs. CD62L is a homing receptor that mediates entry of naïve T cells to peripheral lymph nodes. Maybe the preventing of T cell homing will change the immune response against allogeneic tissue and suppress rejection.
  
  
  METHODS
  We treated different mouse strains with pertussis toxin to manipulate T cell homing and measured the rejection of allografts in terms of allogeneic tumor cells. We transferred pertussis toxin treated or nontreated transgenic T cells into BALB/c wild type mice. The transgenic T cells could be followed ex vivo by specific antibodies. Cytokine production from purified (1x10(5)/ml) T cells after different stimulations in vitro and expression of surface markers on T cells following pertussis toxin treatment by FACS analysis were performed.
  
  
  RESULTS
  Pertussis toxin-treated C57BL/6 mice with the MHC class I molecule H-2K(b) could not reject allogeneic tumor cells R1.1, which expressed the MHC class I molecule H-2K(k) and were killed by these cells. This allograft survival could be demonstrated for various allogeneic cells in different mouse strains with different MHC class I expression and emphasizes the general mechanism in these studies. In vivo CD62L expression on T cells was down-regulated by pertussis toxin in normal mice and transgenic mice that produce only one specific T cell, and after the pertussis toxin treatment the mice showed 4-5 times larger spleens compared to untreated mice. In transfer experiments, we demonstrated that CD62L low transgenic T cells could not home to lymph nodes. Furthermore, spleen cells from pertussis toxin-treated mice produced high amounts of the Th-2 cytokine interleukin 4 after stimulation in primary culture.
  
  
  CONCLUSIONS
  Our data suggest that the inhibition of T cell homing changes the immune response. Prevention of homing of T cells in combination with the induction of a Th-2 response is a mechanism to prevent specific acute rejection of allogeneic tissue.
authors.affiliation: Department of Thoracic Surgery, Albert-Ludwigs-University Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany. christian.stremmel@uniklinik-freiburg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Stremmel
authors.forename: Wulf
authors.initials: W
authors.lastname: Sienel
authors.forename: Stephan
authors.initials: S
authors.lastname: Eggeling
authors.forename: Bernward
authors.initials: B
authors.lastname: Passlick
authors.forename: Anthony
authors.initials: A
authors.lastname: Slavin
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D037342:Pertussis Toxin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D019041:L-Selectin; D037342:Pertussis Toxin