Increased CD4+ T cell infiltrates in rheumatoid arthritis-associated interstitial pneumonitis compared with idiopathic interstitial pneumonitis.
OBJECTIVE
To study lymphocyte markers in rheumatoid arthritis (RA)-associated interstitial pneumonitis (IP) compared with idiopathic IP.


METHODS
Paraffin-embedded lung biopsy specimens from patients with RA (n = 15) and from those without RA (n = 16), all of whom had a diagnosis of either nonspecific IP or usual IP, were studied. Tissue sections from each patient were reviewed by a pathologist, who was blinded to the clinical data. Age and pulmonary function test results were similar in RA and non-RA patients. After high-temperature antigen unmasking, sections were incubated with mouse monoclonal antibodies directed against CD3, CD4, CD8, CD16, and CD20. All slides were coded, and digital images (100x magnification) of the entire tissue area were obtained. Staining was quantified using computer-assisted image analysis.


RESULTS
Staining for CD4 was more prominent in patients with RA than in the non-RA comparison group (median 9.3 cells/mm(2), interquartile range [IQR] 5.5-27.3 versus 0.6 cells/mm(2), IQR 0.2-1.9; P = 0.002). CD4+ cell counts were increased in RA patients with nonspecific IP as well as in RA patients with usual IP, with no major difference between these groups. Results were similar for quantification of CD3 (P = 0.012). There was a less striking trend toward more CD8+ cells in RA patients (P = 0.27 versus those with non-RA lung disease).


CONCLUSIONS
IP lesions in patients with RA are characterized by an increased number of CD4+ cells, as compared with that in patients with idiopathic IP. This finding suggests that CD4+ T cells are critical for the development of pulmonary manifestations in RA, and may have implications for the treatment of RA-associated lung disease.
Turesson
Carl
C
Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. turesson.carl@mayo.edu
Matteson
Eric L
EL
Colby
Thomas V
TV
Vuk-Pavlovic
Zvezdana
Z
Vassallo
Robert
R
Weyand
Cornelia M
CM
Tazelaar
Henry D
HD
Limper
Andrew H
AH
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications*; D017252:CD3 Complex / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D017563:Lung Diseases, Interstitial / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D013194:Staining and Labeling
D017252:CD3 Complex