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This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 290/6/L1087    most recent 00441.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Bruckner, L. Articles by Finkelstein, J. Search for Related Content PubMed PubMed Citation Articles by Bruckner, L. Articles by Finkelstein, J.

Pneumocystis carinii infection sensitizes lung to radiation-induced injury after syngeneic marrow transplantation: role of CD4⁺ T cells

Divisions of ¹Hematology/Oncology/Bone Marrow Transplant, ²Infectious Diseases, and ⁴Neonatology, Departments of Pediatrics and of ⁵Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York; and ³Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana

Submitted 14 October 2005 ; accepted in final form 2 January 2006

A murine model of bone marrow transplant (BMT)-related lung injury was developed to study how infection sensitizes lung to the damaging effects of total body irradiation (TBI) at infectious and TBI doses that individually do not cause injury. Mice infected with Pneumocystis carinii exhibited an asymptomatic, rapid, and transient influx of eosinophils and T cells in bronchoalveolar lavage fluid (BALF). In contrast, mice infected with P. carinii 7 days before receiving TBI and syngeneic BMT (P. carinii/TBI mice) exhibited severe pulmonary dysfunction, surfactant aggregate depletion, and surfactant activity reductions at 17 days post-BMT. BALF from P. carinii/TBI mice contained a disproportionate initial influx of CD4⁺ T cells (CD4⁺:CD8⁺ ratio of 2.7) that correlated with progressive lung injury (from 8 to 17 days post-BMT). Levels of TNF- in BALF were significantly increased in P. carinii/TBI mice compared with mice given either insult alone, with peak values found at 11 days post-BMT. In vivo depletion of CD4⁺ T cells in P. carinii/TBI mice abrogated pulmonary dysfunction and reduced TNF- levels in BALF, whereas depletion of CD8⁺ T cells did not affect lung compliance or TNF-. Lung injury was not attributable to direct P. carinii damage, since CD4-depleted P. carinii/TBI mice that exhibited no injury had higher average lung P. carinii burdens than either mice given P. carinii alone or undepleted P. carinii/TBI mice. Together, these results indicate that P. carinii infection can sensitize the lung to subsequent TBI-mediated lung injury via a process dependent on non-alloreactive CD4⁺ T cells.

idiopathic pneumonia syndrome; pneumonitis; tumor necrosis factor-; inflammation; opportunistic infection; bone marrow transplantation; total body irradiation

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