Restricted junctional diversity of T cell receptor δ gene rearrangements expressed in systemic lupus erythematosus (SLE) patients

Abstract

SLE is an autoimmune connective tissue disorder affecting multiple organs, in which T cells may play a central role. This study investigated T cell receptor (TCR) γ/δ repertoire expression in peripheral blood mononuclear cells (PBMC) of SLE patients and healthy individuals using variable (V) gene family-specific polymerase chain reaction (PCR) amplification of TCR cDNA. The expressed Vγ repertoires were diverse in SLE and control PBMC, although VγIV gene rearrangements were barely detectable or not expressed in some patients. In contrast, δ chain expression was limited in all SLE patients, with S transcripts rearranged primarily to the Vδ1 and Vδ2 genes, as opposed to control PBMC, in which all six Vδ genes were detected. To assess the clonality of TCR populations, cDNA clones containing rearranged Vδ1, Vδ2 and Vγ9 transcripts were sequenced from PBMC of both patients and controls. For controls, δ chain junctional region sequences showed extensive molecular heterogeneity, since virtually all 34 Vδ1 and 32 Vδ2 cDNA clones analysed were unique. A few Vγ9 cDNA clones (3/21) had the same junctional region sequence motif (EVQEL) encoded largely by the Vγ9 and joining (J) γP gene segments. Identical Vγ9 junctional sequences were found in SLE patients that did not contain the EVQEL motif present in normal peripheral blood γ/δ lymphocytes. Moreover, the predominant Vδ1-Jδ-constant (C) δ and Vδ2-Jδ-Cδ gene rearrangements expressed in SLE PBMC showed restricted junctional diversity, but the oligoclonal δ transcripts were different in each patient. These findings suggest in vivo oligoclonal expansion of γ/δ T cells in the periphery of SLE patients in response to a limited number of nominal ligands. Whether γ/δ T cells contribute to the development of systemic autoimmunity remains to be investigated. Show more