Bias toward use of a specific T cell receptor beta-chain variable region in a subgroup of individuals with sarcoidosis.
To evaluate the concept that biases in the usage of T cell antigen receptor beta variable (V) regions may be manifested in T lymphocytes that accumulate in nonmalignant, T cell-mediated human disorders, a V beta 8-specific antibody (anti-Ti3A, 5REX9H5) was used to evaluate lung and blood T cells in pulmonary sarcoidosis, a chronic granulomatous disorder of unknown etiology. Whereas normal patients had less than 5% Ti3A+ lung (n = 7) and/or blood (n = 9) lymphocytes, strikingly, a subgroup (8 of 21) with active pulmonary sarcoidosis had greater than 7% Ti3A+ lung and/or blood T cells and a higher proportion of Ti3A+ lymphocytes in the lung compared with blood. Dual-color flow cytometry demonstrated compartmentalization of Ti3A+ CD4+ lymphocytes to lung and Ti3A+ CD8+ lymphocytes to blood. Analysis with a 32P-labeled V beta 8 probe revealed that sarcoid lung T lymphocytes contained higher amounts of V beta 8+ mRNA than autologous blood T cells. However, Southern analysis of sarcoid lung and blood T cell DNA demonstrated no evidence of clonal rearrangements of V beta 8 genes. These observations demonstrate a clear bias toward the use of at least one V beta region in sarcoidosis, and suggests T cells accumulate secondary to external selective pressure, rather than in a random polyclonal fashion or by clonal expansion of one or few T cell clones.
Moller
D R
DR
Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Konishi
K
K
Kirby
M
M
Balbi
B
B
Crystal
R G
RG
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D000939:Epitopes / Q000032:analysis; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D012507:Sarcoidosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000145:classification / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell