CD4+ T lymphocytes are not necessary for the acute rejection of vascularized mouse lung transplants.
Acute rejection continues to present a major obstacle to successful lung transplantation. Although CD4(+) T lymphocytes are critical for the rejection of some solid organ grafts, the role of CD4(+) T cells in the rejection of lung allografts is largely unknown. In this study, we demonstrate in a novel model of orthotopic vascularized mouse lung transplantation that acute rejection of lung allografts is independent of CD4(+) T cell-mediated allorecognition pathways. CD4(+) T cell-independent rejection occurs in the absence of donor-derived graft-resident hematopoietic APCs. Furthermore, blockade of the CD28/B7 costimulatory pathways attenuates acute lung allograft rejection in the absence of CD4(+) T cells, but does not delay acute rejection when CD4(+) T cells are present. Our results provide new mechanistic insight into the acute rejection of lung allografts and highlight the importance of identifying differences in pathways that regulate the rejection of various organs.
Gelman
Andrew E
AE
Division of Cardiothoracic Surgery, Department of Surgery, Washington University, St Louis, MO 63110, USA.
Okazaki
Mikio
M
Lai
Jiaming
J
Kornfeld
Christopher G
CG
Kreisel
Friederike H
FH
Richardson
Steven B
SB
Sugimoto
Seiichiro
S
Tietjens
Jeremy R
JR
Patterson
G Alexander
GA
Krupnick
Alexander S
AS
Kreisel
Daniel
D
D000208:Acute Disease; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006410:Hematopoiesis / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic; D014184:Transplantation, Homologous / Q000276:immunology
D001324:Autoantigens; D018122:B7-1 Antigen; D018106:CD28 Antigens