Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited

被引:52
作者
Barry, SM
Johnson, MA
Janossy, G
机构
[1] UCL Royal Free & Univ Coll Hosp Med Sch, Dept Immunol, London, England
[2] UCL Royal Free & Univ Coll Hosp Med Sch, Dept Med, London, England
关键词
cytomegalovirus pneumonitis; bronchoalveolar lavage; bone marrow transplantation;
D O I
10.1038/sj.bmt.1702562
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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 mould be aborted by CD4 T cell deficiency in HN infection, However, studies correlating the onset of CR;IV-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 CR;IV 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 mould include the release of tumour necrosis factor-alpha (TNF-alpha) from alveolar macrophages stimulated by interferon-gamma (IFN-gamma) released from NK cells that are reconstituted early after BMT.
引用
收藏
页码:591 / 597
页数:7
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