title: Memory T cells migrate to and reject vascularized cardiac allografts independent of the chemokine receptor CXCR3.
abstract: BACKGROUND
  Memory T cells migrate to and reject transplanted organs without the need for priming in secondary lymphoid tissues, but the mechanisms by which they do so are not known. Here, we tested whether CXCR3, implicated in the homing of effector T cells to sites of infection, is critical for memory T-cell migration to vascularized allografts.
  
  
  METHODS
  CD4 and CD8 memory T cells were sorted from alloimmunized CXCR3 and wildtype B6 mice and cotransferred to congenic B6 recipients of BALB/c heart allografts. Graft-infiltrating T cells were quantitated 20 and 72 hr later by flow cytometry. Migration and allograft survival were also studied in splenectomized alymphoplastic (aly/aly) recipients, which lack secondary lymphoid tissues.
  
  
  RESULTS
  We found that polyclonal and antigen-specific memory T cells express high levels of CXCR3. No difference in migration of wildtype versus CXCR3 CD4 and CD8 memory T cells to allografts could be detected in wildtype or aly/aly hosts. In the latter, wildtype and CXCR3 memory T cells precipitated acute rejection at similar rates. Blocking CCR5, a chemokine receptor also upregulated on memory T cells, did not delay graft rejection mediated by CXCR3 memory T cells.
  
  
  CONCLUSIONS
  CXCR3 is not critical for the migration of memory T cells to vascularized organ allografts. Blocking CXCR3 or CXCR3 and CCR5 does not delay acute rejection mediated by memory T cells. These findings suggest that the mechanisms of memory T cell-homing to transplanted organs may be distinct from those required for their migration to sites of infection.
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Oberbarnscheidt
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Walch
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Williams
authors.forename: John T
authors.initials: JT
authors.lastname: Walters
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Hoffman
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Camirand
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Lakkis
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019713:Receptors, CCR5 / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013156:Splenectomy; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D015815:Cell Adhesion Molecules; C515188:Cxcr3 protein, mouse; D019713:Receptors, CCR5; D054367:Receptors, CXCR3