Chest
Volume 92, Issue 3, September 1987, Pages 547-549
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Hypotheses
Lung Immunogenicity, Rejection, and Obliterative Bronchiolitis

https://doi.org/10.1378/chest.92.3.547Get rights and content

Evidence suggests that obliterative bronchiolitis (OB) following human heart-lung transplantation is a form of allograft rejection related to augmented expression of class II major histocompatibility complex antigens (MHCII) on airway epithelium and mediated by activated T cells. Other forms of OB, including those related to viral infection and autoimmune disease, may reflect a similar mechanism.

Section snippets

LUNG IMMUNOGENICITY

It is generally accepted that the immunogenicity of allografts depends on their expression of class II major histocompatibility complex antigens (MHCII). Recognition of donor (foreign) class II antigens by recipient lymphocytes results in the generation of allospecific activated helper T lymphocytes, which then mediate graft rejection.9 Allograft rejection is therefore stimulated by the expression of MHCII antigens and effected by activated T cells. In general, these considerations suggest that

HYPOTHESIS

These considerations may be relevant to the development of OB in the transplanted lung. Unlike other transplanted organs, the lung is subjected to a continuous bombardment of antigenic stimuli (both infective and noninfective) from the ambient air, and current evidence suggests that microaspiration of pharyngeal flora occurs commonly in normal subjects.12 The prevalence of viruses suggests that viral inhalation or aspiration with γ-interferon generation must be a common event. It may be

DISCUSSION

Experimental evidence that MHCII expression is necessary for activation of allograft specific helper T lymphocytes,9 together with preliminary evidence in rats showing MHCII expression associated with rejection14 and a recent clinical study in renal transplant10 recipients, suggests that MHCII expression may prove to be a sensitive index of lung rejection. No data are currently available to evaluate the specificity of such a finding. While a wide variety of stimuli are now known to upregulate

CONCLUSION

A reduction in allograft immunogenicity may be as effective as attenuation of the effector response in the treatment of rejection, and the recently documented effect of cyclosporin and corticosteroids in reducing MHCII expression may be an important component of their antirejection action.11 Specifically, airway disease following lung transplantation may be related to upregulation of MHCII on bronchial epithelium, and monitoring of MHCII expression may provide both a sensitive index of

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Supported by a grant from the Leah and Samuel Osher Medical Education Foundation.

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