Selective early increases of bronchoalveolar CD8+ lymphocytes in a LEW rat model of hypersensitivity pneumonitis.
BACKGROUND
The pathogenesis of hypersensitivity pneumonitis (HP) involves cell-mediated hypersensitivity; various bronchoalveolar T-cell subsets with uncertain roles in disease have been reported and implicated in the pathogenesis.


OBJECTIVE
Previous studies at 72 hours after initial antigen challenges showed proportionate increases in T-cell phenotypes. Therefore we tested the hypothesis that early events in response to inhaled antigen in a LEW rat model of HP would include a disproportionate appearance in bronchoalveolar lavage fluid (BALF) and lung parenchyma of a specific T-effector cell responsible for subsequent inflammation and that these events could be identified by phenotyping.


METHODS
We double labeled BALF and parenchymal lung lymphocytes with monoclonal antibodies and used flow cytometry to quantitate CD4+ and CD8+ phenotypic subsets 4 and 24 hours after inhalation of antigen.


RESULTS
We found disproportionate increases in BALF CD8+ phenotypes. The strongest correlation with pathologic findings was for a putative cytotoxic effector (CD8+CD45R-) T lymphocyte.


CONCLUSIONS
Meaningful interpretation of lung T-cell phenotype quantitation requires studies of kinetics of cellular influxes, timing after antigen challenge, and relative comparison with increases in other phenotypes. Any pathogenetic role assigned to a phenotype must also await functional studies, including cytokine generation and secretion and cell-cell interactions in situ.
Richerson
H B
HB
Department of Internal Medicine, University of Iowa Hospitals, Iowa City 52242-1081, USA.
Coon
J D
JD
Lubaroff
D
D
D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D005260:Female; D016130:Immunophenotyping; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000502:physiology