[Immunopathology of cytomegalovirus pneumonia and allograft rejection in lung transplantation. Group of Pulmonary Transplantation of the University Paris-Sud].
In order to better understand the immunopathology of acute complications of lung transplantation we have analysed the different parameters of cytotoxic cell and macrophage activation during the course of pulmonary allograft rejection and cytomegalovirus pneumonia. In transplanted patients presenting with an acute pulmonary allograft rejection, a cytomegalovirus pneumonia or no complication (control group), we have studied, first serum markers of immune activation: interleukin-2 soluble receptor (IL-2sR), neopterin, IL-6, TNF soluble receptors (TNF-sR55 and TNF-sR75). Secondly the intrapulmonary compartmentalisation of allogenic and antiviral responses were evaluated by studying bronchoalveolar lavage fluid (BAL). The level of IL-6 was measured in BAL supernatants and the gene expression of two cytokines (IL-1 beta and IL-6) and two markers of activated cytotoxic cells (granzyme B and perforin) were studied by in situ hybridisation on the alveolar cells. Acute pulmonary allograft rejection was characterised by the paucity of systemic stigmata of immune activation and by the intrapulmonary compartmentalisation of the inflammatory response principally expressed by an increase in alveolar concentration of IL-6, TNF-sR55 and TNF-sR75, and an increased expression of the IL-1 beta gene. Cytomegalovirus pneumonia is accompanied by an intense local and systemic inflammatory activity as evidenced by the serum level of IL-2sR, neopterin, TNF-sR55 and TNF-sR75, the alveolar concentration of IL-6, TNF-sR55 and TNF-sR75, and the expression of monokine (IL-1 beta, IL-6) and of cytotoxic mediator (granzyme b, perforin) genes by BAL cells. These mediators could participate in the elaboration of an acute or chronic inflammatory response which would be potentially deleterious for the graft.
Service de Pneumologie, Hôpital Antoine-Béclère, Clamart.
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Humbert
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Emilie
D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000032:analysis; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology*; D015870:Gene Expression; D006084:Graft Rejection; D053804:Granzymes; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics; D015850:Interleukin-6 / Q000032:analysis; D016040:Lung Transplantation / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D019798:Neopterin; D054353:Perforin; D011024:Pneumonia, Viral / Q000276:immunology* / Q000473:pathology*; D052899:Pore Forming Cytotoxic Proteins; D011650:Pulmonary Alveoli / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics; D014184:Transplantation, Homologous
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D054353:Perforin; D001708:Biopterins; D019798:Neopterin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases
Immunopathologie des pneumopathies à cytomégalovirus et des rejets d'allogreffes chez le transplanté pulmonaire. Groupe de Transplantation Pulmonaire de l'Université Paris-Sud.