RESTRICTED JUNCTIONAL DIVERSITY OF T-CELL RECEPTOR DELTA-GENE REARRANGEMENTS EXPRESSED IN SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE) PATIENTS

SLE is an autoimmune connective tissue disorder affecting multiple org ans, in which T cells may play a central role. This study investigated T cell receptor (TCR) gamma/delta repertoire expression in peripheral blood mononuclear cells (PBMC) of SLE patients and healthy individual s using variable (V) gene family-specific polymerase chain reaction (P CR) amplification of TCR cDNA. The expressed V gamma repertoires were diverse in SLE and control PBMC, although V gamma IV gene rearrangemen ts were barely detectable or not expressed in some patients. In contra st, delta chain expression was limited in all SLE patients, with delta transcripts rearranged primarily to the V delta 1 and V delta 2 genes , as opposed to control PBMC, in which all six V delta genes were dete cted. To assess the clonality of TCR populations, cDNA clones containi ng rearranged V delta 1, V delta 2 and V gamma 9 transcripts were sequ enced from PBMC of both patients and controls. For controls, delta cha in junctional region sequences showed extensive molecular heterogeneit y, since virtually all 34 V delta 1 and 32 V delta 2 cDNA clones analy sed were unique. A few V gamma 9 cDNA clones (3/21) had the same junct ional region sequence motif (EVQEL) encoded largely by the V gamma 9 a nd joining (J) gamma P gene segments. Identical V gamma 9 junctional s equences were found in SLE patients that did not contain the EVQEL mot if present in normal peripheral blood gamma/delta lymphocytes. Moreove r, the predominant V delta 1-J delta-constant (C) delta and V delta 2- J delta-C delta gene rearrangements expressed in SLE PBMC showed restr icted junctional diversity, but the oligoclonal delta transcripts were different in each patient. These findings suggest in vivo oligoclonal expansion of gamma/delta T cells in the periphery of SLE patients in response to a limited number of nominal ligands. Whether gamma/delta T cells contribute to the development of systemic autoimmunity remains to be investigated.