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Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited

Various hypotheses have been proposed to explain why cytomegalovirus pneumonitis (CMV-P) is frequent and severe in bone marrow transplant patients while remaining rare and mild in HIV infected patients. One hypothesis suggests that CMV-P is an immunopathological condition that is common in bone marr...

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Autores principales: Barry, SM, Johnson, MA, Janossy, G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101863/
https://www.ncbi.nlm.nih.gov/pubmed/11035367
http://dx.doi.org/10.1038/sj.bmt.1702562
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author Barry, SM
Johnson, MA
Janossy, G
author_facet Barry, SM
Johnson, MA
Janossy, G
author_sort Barry, SM
collection PubMed
description Various hypotheses have been proposed to explain why cytomegalovirus pneumonitis (CMV-P) is frequent and severe in bone marrow transplant patients while remaining rare and mild in HIV infected patients. One hypothesis suggests that CMV-P is an immunopathological condition that is common in bone marrow transplantation (BMT) under the effects of an abnormally regenerating immune system that reacts against CMV infected lung tissue. Such a hypothesis implicates CD4 T lymphocytes as one of the critical cell populations involved in immunopathology and also suggests that this process would be aborted by CD4 T cell deficiency in HIV infection. However, studies correlating the onset of CMV-P with lymphocyte reconstitution following BMT have revealed that CD4 cells are present at very low frequencies in the blood during the early period after transplantation when most cases of CMV-P occur. Furthermore, studies directly investigating bronchoalveolar lavage cell types during episodes of CMV-P in BMT patients have also failed to demonstrate significant CD4 involvement and, instead, have emphasized a predominance of natural killer (NK) cells and CD8 cells. These findings serve as the basis for questioning the validity of a CD4-driven immunopathological model of CMV-P in BMT. On the other hand, a variety of experimental and clinical observations support the protective role of CMV-specific CD3(+) CD8 T lymphocytes against CMV in both immunocompetent individuals and BMT patients. In a murine BMT model, adoptive transfer of syngeneic BM cells was associated with massive increases in lung CD8 cells which resulted in the resolution rather than the exacerbation of existing CMV-P. In the light of these findings a more plausible hypothesis for CMV-P in BMT is that during the early period after transplantation adequate protective CD8 responses are absent and an uncontrolled CMV proliferation is allowed to develop. Once a critical viral load is reached a cytokine ‘storm’ may be triggered in the lung tissue that aggravates direct CMV-associated cytopathic effects. Likely candidates for this process would include the release of tumour necrosis factor-alpha (TNF-α) from alveolar macrophages stimulated by interferon-gamma (IFN-γ) released from NK cells that are reconstituted early after BMT. Bone Marrow Transplantation (2000) 26, 591–597.
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spelling pubmed-71018632020-03-31 Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited Barry, SM Johnson, MA Janossy, G Bone Marrow Transplant Article Various hypotheses have been proposed to explain why cytomegalovirus pneumonitis (CMV-P) is frequent and severe in bone marrow transplant patients while remaining rare and mild in HIV infected patients. One hypothesis suggests that CMV-P is an immunopathological condition that is common in bone marrow transplantation (BMT) under the effects of an abnormally regenerating immune system that reacts against CMV infected lung tissue. Such a hypothesis implicates CD4 T lymphocytes as one of the critical cell populations involved in immunopathology and also suggests that this process would be aborted by CD4 T cell deficiency in HIV infection. However, studies correlating the onset of CMV-P with lymphocyte reconstitution following BMT have revealed that CD4 cells are present at very low frequencies in the blood during the early period after transplantation when most cases of CMV-P occur. Furthermore, studies directly investigating bronchoalveolar lavage cell types during episodes of CMV-P in BMT patients have also failed to demonstrate significant CD4 involvement and, instead, have emphasized a predominance of natural killer (NK) cells and CD8 cells. These findings serve as the basis for questioning the validity of a CD4-driven immunopathological model of CMV-P in BMT. On the other hand, a variety of experimental and clinical observations support the protective role of CMV-specific CD3(+) CD8 T lymphocytes against CMV in both immunocompetent individuals and BMT patients. In a murine BMT model, adoptive transfer of syngeneic BM cells was associated with massive increases in lung CD8 cells which resulted in the resolution rather than the exacerbation of existing CMV-P. In the light of these findings a more plausible hypothesis for CMV-P in BMT is that during the early period after transplantation adequate protective CD8 responses are absent and an uncontrolled CMV proliferation is allowed to develop. Once a critical viral load is reached a cytokine ‘storm’ may be triggered in the lung tissue that aggravates direct CMV-associated cytopathic effects. Likely candidates for this process would include the release of tumour necrosis factor-alpha (TNF-α) from alveolar macrophages stimulated by interferon-gamma (IFN-γ) released from NK cells that are reconstituted early after BMT. Bone Marrow Transplantation (2000) 26, 591–597. Nature Publishing Group UK 2000-09-15 2000 /pmc/articles/PMC7101863/ /pubmed/11035367 http://dx.doi.org/10.1038/sj.bmt.1702562 Text en © Macmillan Publishers Limited 2000 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Barry, SM
Johnson, MA
Janossy, G
Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited
title Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited
title_full Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited
title_fullStr Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited
title_full_unstemmed Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited
title_short Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited
title_sort cytopathology or immunopathology? the puzzle of cytomegalovirus pneumonitis revisited
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101863/
https://www.ncbi.nlm.nih.gov/pubmed/11035367
http://dx.doi.org/10.1038/sj.bmt.1702562
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