Allogeneic bronchoalveolar lavage cells induce the histology of acute lung allograft rejection, and deposition of IgG2a in recipient murine lungs.
The immunologic and histologic changes associated with lung allograft rejection are believed to result from the presentation of donor lung alloantigens to recipient lymphocytes resulting in up-regulated Th1 lymphocyte activity. The ability of allogeneic lung immune cells to induce the pathologic and immunologic changes associated with acute lung allograft rejection are unknown. The current study determined whether allogeneic (C57BL/6, I-a(b)) bronchoalveolar lavage (BAL) cells (> or = 97% macrophages), when instilled into the lungs of recipient BALB/c mice (I-a(d)), induced the histology and immunology associated with acute lung allograft rejection. BALB/c mice received BAL cells from either C57BL/6 mice (allogeneic instillate) or BALB/c mice (autologous instillate) or PBS (control) by nasal insufflation weekly for 4 wk. Allogeneic BAL cells resulted in a lymphocytic bronchitis and vasculitis analogous to grade 1 to 2 lung allograft rejection. The mice given allogeneic instillates had a greater percentage of lymphocytes in the BAL fluid than those given autologous instillates. After instillation of allogeneic BAL cells, the Th1 cytokines, IL-2 and IFN-gamma (IFN-gamma), were produced locally in greater quantities and more frequently than Th2 cytokine IL-10. IL-4, another Th2 cytokine, was not detected. The local production of IgG1 and IgG2a, which are dependent on IL-4 and IFN-gamma, respectively, were increased. However, only IgG2a was deposited in the perivascular and peribronchiolar tissues. These data show that installation of allogeneic BAL cells into the airways of recipient mice induced up-regulated Th1 lymphocyte activity and caused the histologic changes associated with lung allograft rejection.
Wilkes
D S
DS
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.
Heidler
K M
KM
Bowen
L K
LK
Quinlan
W M
WM
Doyle
N A
NA
Cummings
O W
OW
Doerschuk
C M
CM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016207:Cytokines / Q000032:analysis; D006084:Graft Rejection / Q000473:pathology*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous / Q000473:pathology*
D016207:Cytokines; D007074:Immunoglobulin G