T-lymphocytes that accumulate in the lung in sarcoidosis have evidence of recent stimulation of the T-cell antigen receptor.
Sarcoidosis, a granulomatous disease of unknown etiology, is characterized at sites of disease such as the lung by the accumulation of large numbers of T-lymphocytes. To differentiate whether the T-cells accumulate in organs nonspecifically (e.g., through chemotaxis or tumorlike proliferation) or more specifically through an antigen-driven ordered immune response, the present study capitalized on the knowledge that specific antigen stimulation of T-cells requires antigen interactions with the T-cell antigen receptor (TCR), resulting in a decrease in the number of surface TCR and a concomitant increase in TCR mRNA levels, i.e., if lung T-cell accumulation in pulmonary sarcoid results from an ordered immune response, lung, but not blood, T-cells should demonstrate evidence of recent triggering of the alpha beta receptor, the most abundant type of TCR. The surface density of T-cell surface alpha beta TCR expression was evaluated by flow cytometry with an anti-alpha beta antibody and TCR beta-chain mRNA transcript number quantified by in situ hybridization with 35S-labeled antisense and sense cRNA probes. Control studies utilizing normal blood T-lymphocytes stimulated with the anti-CD3 monoclonal antibody, OKT3, in the presence of autologous monocytes, demonstrated the expected down-regulation of surface alpha beta TCR expression and increased beta-chain mRNA transcript number. When lung and blood T-cells of patients with pulmonary sarcoidosis were compared immediately upon recovery (i.e., without in vitro stimulation), the lung T-cells of 10 of 10 subjects demonstrated a decreased surface density of alpha beta TCR compared with their autologous blood T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Du Bois
R M
RM
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Kirby
M
M
Balbi
B
B
Saltini
C
C
Crystal
R G
RG
D000328:Adult; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008168:Lung / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology*; D008297:Male; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D012507:Sarcoidosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta