Bias toward use of a specific T cell receptor beta-chain variable region in a subgroup of individuals with sarcoidosis.
| Publication Type | Academic Article |
| Authors | Moller D, Konishi K, Kirby M, Balbi B, Crystal R |
| Journal | J Clin Invest |
| Volume | 82 |
| Issue | 4 |
| Pagination | 1183-91 |
| Date Published | 10/01/1988 |
| ISSN | 0021-9738 |
| Keywords | Immunoglobulin Variable Region, Receptors, Antigen, T-Cell, Sarcoidosis, T-Lymphocytes |
| Abstract | 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. |
| DOI | 10.1172/JCI113715 |
| PubMed ID | 2459159 |
| PubMed Central ID | PMC442668 |