Selective reduction and recovery of invariant Valpha24JalphaQ T cell receptor T cells in correlation with disease activity in patients with systemic lupus erythematosus.

Abstract

To study the regulatory role of CD4-CD8- double-negative (DN) invariant T cell receptor (TCR) Valpha24JalphaQ T cells, a human counterpart of murine NK 1 + T cells, in the autoimmune process of systemic lupus erythematosus (SLE). We carried out a 2 step frequency analysis of DN Valpha24JalphaQ T cells in patients with SLE before and after prednisolone therapy; the frequency of DN Valpha24+ T cells was determined by 3 color FACS analysis and subsequently the frequency of Valpha24JalphaQ rearrangement among DN Valpha24+ T cells was determined by sequencing. DN Valpha24+ T cells were significantly increased in patients with active SLE compared to healthy subjects. In healthy subjects, invariant Valpha24JalphaQ TCR dominated in DN Valpha24+ T cells at a high frequency (93-100%). However, the invariant Valpha24JalphaQ TCR was not detected in DN Valpha24+ T cells from patients with active SLE, and instead 2 to 9 Jalpha genes other than the invariant JalphaQ were oligoclonally expanded in the patients. In inactive SLE induced by prednisolone therapy, the invariant Valpha24JalphaQ TCR could be detected in DN Valpha24+ T cells from all the patients and dominated in most of the patients. Further, oligoclonally expanded Valpha24+ clones other than the invariant JalphaQ gene in active disease states were significantly decreased by prednisolone therapy. The selective reduction of DN invariant Valpha24JalphaQ T cells is related to the disease progression of SLE, while DN TCR Valpha24 T cells other than Valpha24JalphaQ T cells constitute autoaggressive T cells in SLE.