Acute hypersensitivity pneumonitis

Serial changes in lung lymphocyte subpopulations after exposure to antigen

J. Bernardo, G. W. Hunninghake, J. E. Gadek, V. J. Ferrans, Ronald Crystal

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The earliest lesion in hypersensitivity pneumonitis is an acute inflammatory alveolitis characterized by parenchymal hemorrhage and accumulation of polymorphonuclear leukocytes within the lung. In many instances, this initial lesion is replaced by a more chronic alveolitis, with development of mononuclear cell interstitial infiltrate, granuloma formation, and interstitial fibrosi. To help define the mechanisms by which the early polymorphonuclear leukocyte alveolitis of acute hypersensitivity pneumonitis evolves into a chronic mononuclear-cell process, an animal model of the disease was developed using guinea pigs sensitized by footpad injection with either ovalbumin (OVA) in complete Freund's adjuvant (CFA), CFA alone, or phosphate-buffered saline. Ten days after sensitization, the animals were challenged by intratracheal injection of either particular OVA, particulate human serum albumin, or phosphate-buffered saline alone, and their lungs were evaluated sequentially for changes in histologic appearance and lymphocyte subpopulations. After challenge, only animals sensitized with CFA plus OVA and challenged with particulate OVA developed pulmonary lesions consistent with acute hypersensitivity pneumonitis. Within 4 h after challenge, these animals developed an acute hemorrhagic alveolitis that persisted for more than 24 h. By 48 to 96 h, the alveolitis evolved into a predominantly mononuclear-cell infiltrate. This change in the histologic appearance of the lungs in these animals was preceded by a rapid increase in the proportions of T-lymphocytes within the lungs, noted by 24 h after intractracheal challenge with specific antigen. Before intratracheal challenge with antigen, lung lymphocytes from only the group of animals immunized with CFA plus OVA were capable of proliferating on exposure to OVA in vitro. In the same group, lymphocytes recovered from the lung after intratracheal particulate OVA demonstrated blast transformation in vivo, a phenomenon not found in any other group. These studies suggest that the alveolitis of acute hypersensitivity pneumonitis is rapidly associated with changes in populations of immune effector cells before development of tho mononuclear cell alveolitis characteristic of the chronic disease.

Original languageEnglish
Pages (from-to)985-994
Number of pages10
JournalAmerican Review of Respiratory Disease
Volume120
Issue number5
Publication statusPublished - 1 Dec 1979
Externally publishedYes

Fingerprint

Extrinsic Allergic Alveolitis
Lymphocyte Subsets
Ovalbumin
Freund's Adjuvant
Antigens
Lung
Neutrophils
Phosphates
Lymphocytes
Animal Disease Models
Injections
Lymphocyte Activation
Granuloma
Serum Albumin
Guinea Pigs
Chronic Disease
Hemorrhage
T-Lymphocytes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Acute hypersensitivity pneumonitis : Serial changes in lung lymphocyte subpopulations after exposure to antigen. / Bernardo, J.; Hunninghake, G. W.; Gadek, J. E.; Ferrans, V. J.; Crystal, Ronald.

In: American Review of Respiratory Disease, Vol. 120, No. 5, 01.12.1979, p. 985-994.

Research output: Contribution to journalArticle

Bernardo, J. ; Hunninghake, G. W. ; Gadek, J. E. ; Ferrans, V. J. ; Crystal, Ronald. / Acute hypersensitivity pneumonitis : Serial changes in lung lymphocyte subpopulations after exposure to antigen. In: American Review of Respiratory Disease. 1979 ; Vol. 120, No. 5. pp. 985-994.
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