Selective reduction and recovery of invariant V alpha 24Ja alpha Q T cell receptor T cells in correlation with disease activity in patients with systemic lupus erythematosus

Objective. To study the regulatory role of CD4-CD8-double-negative (DN) inv ariant T cell receptor (TCR) V alpha 24J alphaQ T cells, a human counterpar t of murine NK1+ T cells, in the autoimmune process of systemic lupus eryth ematosus (SLE). Methods. We carried out a 2 step frequency analysis of DN V alpha 24J alpha Q T cells in patients with SLE before and after prednisolone therapy, the f requency of DN V alpha 24+ 7 cells was determined by 3 color FACS analysis and subsequently the frequency of V alpha 24J alphaQ rearrangement among DN V alpha 24+ T cells was determined by sequencing. Results. DN V alpha 24+ T cells were significantly increased in patients wi th active SLE compared to healthy subjects. In healthy subjects, invariant V alpha 24J alphaQ TCR dominated in DN V alpha 24+ T cells at a high freque ncy (93-100%). However, the invariant V alpha 24J alphaQ TCR was not detect ed in DN V alpha 24+ T cells from patients with active SLE, and instead 2 t o 9 J alpha genes other than the invariant J alphaQ were oligoclonally expa nded in the patients. In inactive SLE induced by prednisolone therapy, the invariant V alpha 24J alphaQ TCR could be detected in DN V alpha 24+ T cell s from all the patients and dominated in most of the patients. Further, oli goclonally expanded V alpha 24+ clones other than the invariant J alphaQ ge ne in active disease states were significantly decreased by prednisolone th erapy. Conclusion. The selective reduction of DN invariant V alpha 24J alphaQ T ce lls is related to the disease progression of SLE, while DN TCR V alpha 24 T cells other than V alpha 24J alphaQ T cells constitute autoaggressive T ce lls in SLE.