Association of γδ T Cell Compartment Size to Disease Activity and Response to Therapy in SLE

OBJECTIVE: Although γδT cells are widely recognized as pivotal elements in immune-mediated diseases, their role in the pathogenesis of SLE and therapeutic outcome remains under explored. The current study aims to characterize the γδT cell compartment in SLE and correlate its status to disease severity and response to therapy. METHODS: Human peripheral blood-derived γδ T cells were isolated from 14 healthy volunteers and 22 SLE patients (before and after 4 and 12 weeks following the onset of glucocorticoids (GC), mycophenolatemofetil (MMF) orhydroxychloroquine (HCQ) treatment). The γδ T cells were characterized using flow cytometry. In addition, serum concentration of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A was determined by cytometric bead array (CBA). RESULTS: The SLEDAI scores dropped significantly following therapy in a subset of patients (responders–R) but not in some (non- responders–NR). Peripheral blood γδ T cells in general, and γ9(+)δ T cells and TNF-α/IL-17-secreting CD4(-)CD8(-)γδ T cell subsets in particular, were decreased in SLE compared to healthy controls. The numbers of the γδ T cell subsets reached levels similar to those of healthy controls following therapy in R but not in NR. Serum IL-6, IL-10 and IL-17 but not IFN-γ and TNF-α were significantly increased in SLE compared to the healthy controls and exhibited differential changes following therapy. In addition, inverse correlation was observed between SLEDAI scores and γδ T cell compartments, especially with TNF-α(+)γδT cells, TNF-α(+)γ9+δT cells and IL17(+)CD4(-)CD8(-)γδT cells subsets. Differential correlation patterns were also observed between serum cytokine levels and various γδ T cell compartments. CONCLUSIONS: A strong association exists between γδ T cell compartments and SLE pathogenesis, disease severity and response to therapy.