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Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited

Bone Marrow Transplantation volume 26, pages 591–597 (2000)Cite this article

Abstract

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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Acknowledgements

We thank Profs HG Prentice, MJ Reddehase, A Madrigal and P Griffiths and Dr J Grundy for help and critical reading of the manuscript.

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  1. Department of Immunology, Royal Free and University College Hospital Medical School, London, UK

    SM Barry & G Janossy

  2. Department of Medicine, Royal Free and University College Hospital Medical School, London, UK

    SM Barry & MA Johnson

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Barry, S., Johnson, M. & Janossy, G. Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited. Bone Marrow Transplant 26, 591–597 (2000). https://doi.org/10.1038/sj.bmt.1702562

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