The role of T cells in infection-driven interstitial pneumonia after bone marrow transplantation in mice.
Over the course of five weeks, there were no significant histopathological changes in the lungs of mice given either allogeneic or syngeneic bone marrow transplants (BMT) with whole body irradiation (WBI). However, all mice that received both WBI and Pneumocystis carinii inoculation developed a more protracted and severe interstitial pneumonia than that of normal mice given P carinii. This pneumonia was exacerbated by allogeneic BMT but was ameliorated by syngeneic BMT. The interstitial pneumonia caused by allogeneic BMT and P carinii infection was associated with the influx of large numbers of activated CD4+ cells of donor origin. Depletion of CD4+ T cells in vivo in these mice inhibited both the development of graft-versus-host disease (GVHD) and the interstitial pneumonia. In vitro depletion of T cells before allogeneic BMT and P carinii infection also inhibited GVHD-however, it did not stop the development of interstitial pneumonia caused by the infiltration of host-derived T cells. These results indicate that in this model infection is required for development of interstitial pneumonia after allogeneic BMT. This interstitial pneumonia can be caused by the accumulation of CD4+ cells of either donor or recipient origin but not by CD8+ cells. The accumulation of these cells in lungs of normal mice in response to P carinii does not cause interstitial pneumonia, but irradiation of the host before the cellular accumulation does. This interstitial pneumonia can occur in infected mice after either syngeneic or allogeneic BMT, but is exacerbated by GVHD.
Garvy
B A
BA
Trudeau Institute, Inc., Saranac Lake, New York 12983, USA.
Harmsen
A G
AG
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D016867:Immunocompromised Host; D016130:Immunophenotyping; D008168:Lung / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D011010:Pneumocystis / Q000276:immunology; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000473:pathology; D014916:Whole-Body Irradiation