Dual effects of the alloresponse by Th1 and Th2 cells on acute and chronic rejection of allotransplants.
The contribution of direct and indirect alloresponses by CD4(+) Th1 and Th2 cells in acute and chronic rejection of allogeneic transplants remains unclear. In the present study, we addressed this question using a transplant model in a single MHC class I-disparate donor-recipient mouse combination. BALB/c-dm2 (dm2) mutant mice do not express MHC class I L(d) molecules and reject acutely L(d+) skin grafts from BALB/c mice. In contrast, BALB/c hearts placed in dm2 mice are permanently accepted in the absence of chronic allograft vasculopathy. In this model, CD4(+) T cells are activated following recognition of a donor MHC class I determinant, L(d) 61-80, presented by MHC Class II A(d) molecules on donor and recipient APC. Pre-transplantation of recipients with L(d) 61-80 peptide emulsified in complete Freund's adjuvant induced a Th1 response, which accelerated the rejection of skin allografts, but it had no effect on cardiac transplants. In contrast, induction of a Th2 response to the same peptide abrogated the CD8(+) cytotoxic T cells response and markedly delayed the rejection of skin allografts while it induced de novo chronic rejection of heart transplants. This shows that Th2 cells activated via indirect allorecognition can exert dual effects on acute and chronic rejection of allogeneic transplants.
Illigens
Ben M
BM
Cellular and Molecular Immunology Laboratory, Transplantation Unit, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02114, USA.
Yamada
Akira
A
Anosova
Natalie
N
Dong
Victor M
VM
Sayegh
Mohamed H
MH
Benichou
Gilles
G
D000818:Animals; D002908:Chronic Disease; D006084:Graft Rejection / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D016038:Skin Transplantation / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I