title: Graft rejection mediated by CD4+ T cells via indirect recognition of alloantigen is associated with a dominant Th2 response.
abstract: CD4(+) T cells that respond to indirectly presented alloantigen have been shown to mediate chronic rejection, however, the role of the indirect pathway in acute rejection has yet to be completely elucidated. To this end, BALB/c or C57BL/6 mice were depleted of CD8(+) T cells and transplanted with class II transactivator (CIITA)-deficient cardiac allografts, which cannot directly present class II alloantigens to CD4(+) T cells. In this manner, the rejection response by CD4(+) cells was forced to rely upon the indirect recognition pathway. When not depleted of CD8(+) cells, both BALB/c and C57BL/6 mice rejected CIITA-/- allografts and a polarized Th1 response was observed. In contrast, when BALB/c recipients of CIITA-/- allografts were depleted of CD8(+) T cells, the grafts were acutely rejected and a strong Th2 response characterized by eosinophil influx into the graft was observed. Interestingly, CD8-depleted C57BL/6 recipients of CIITA-/- allografts did not acutely reject their transplants and a Th2 response was not mounted. These findings indicate that CD4(+) T cells responding to indirectly presented alloantigens mediate graft rejection in a Th2-dominant manner, and provide further evidence for the role of Th2 responses in acute graft rejection.
authors.affiliation: Department of Surgery, Section of General Surgery, University of Michigan School of Medicine, Ann Arbor, USA.
authors.forename: Keri
authors.initials: K
authors.lastname: Csencsits
authors.forename: Sherri Chan
authors.initials: SC
authors.lastname: Wood
authors.forename: Guanyi
authors.initials: G
authors.lastname: Lu
authors.forename: John C
authors.initials: JC
authors.lastname: Magee
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Eichwald
authors.forename: Cheong-Hee
authors.initials: CH
authors.lastname: Chang
authors.forename: D Keith
authors.initials: DK
authors.lastname: Bishop
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009687:Nuclear Proteins / Q000172:deficiency; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000172:deficiency; D016042:Transplantation, Heterotopic / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D007519:Isoantigens; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators