T-cell receptor variable region gene usage by CD4+ and CD8+ T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients.
Sarcoidosis is a chronic noncaseating granulomatous disease of unknown etiology. An accumulation of CD4+ T cells in the alveolar space of the lungs is a characteristic feature of the disease. We have in this study analyzed T-cell receptor (TCR) variable region (V) gene usage by CD4+ and CD8+ lung and peripheral blood T cells of 29 sarcoidosis patients and 15 control subjects. In the patient group, we found a 100% positive correlation between TCR V alpha 2.3+ CD4+ lung T-cell expansions and the expression of the HLA-DR3(17),DQ2 haplotype. The remaining TCR V alpha/V beta gene products analyzed in this study--V alpha 12, V beta 2, V beta 3, V beta 5.1, V beta 5.2/5.3, V beta 5.3, V beta 6.7, V beta 8.1, and V beta 12--were in general normally expressed by CD4+ T cells, although some of them were used to a significantly higher or lower degree by lung T cells compared to peripheral blood T cells. We also performed repeated TCR V gene analyses on some HLA-DR3+ patients and found an association between the ratio bronchoalveolar lavage fluid/peripheral blood V alpha 2.3+ CD4+ T cells and clinical signs of disease activity. Finally, when analyzing TCR V gene usage by CD8+ bronchoalveolar lavage fluid and peripheral blood T cells, a normal V alpha 2.3 usage was found in all cases, but lung-restricted T-cell expansions using other TCR V gene segment products were identified.
Grunewald
J
J
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
Olerup
O
O
Persson
U
U
Ohrn
M B
MB
Wigzell
H
H
Eklund
A
A
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens; D005260:Female; D006680:HLA Antigens / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012507:Sarcoidosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D016827:CD8 Antigens; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell