Association Of Gamma Delta T Cell Compartment Size To Disease Activity And Response To Therapy In Sle

ObjectiveAlthough gamma delta T 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 gamma delta T cell compartment in SLE and correlate its status to disease severity and response to therapy.MethodsHuman peripheral blood-derived gamma delta 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 gamma delta T cells were characterized using flow cytometry. In addition, serum concentration of IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-10 and IL-17A was determined by cytometric bead array (CBA).ResultsThe SLEDAI scores dropped significantly following therapy in a subset of patients (responders-R) but not in some (non-responders-NR). Peripheral blood gamma delta T cells in general, and gamma 9+delta T cells and TNF-alpha/IL-17-secreting CD4(-)CD8(-)gamma delta T cell subsets in particular, were decreased in SLE compared to healthy controls. The numbers of the gamma delta 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-gamma and TNF-alpha 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 gamma delta T cell compartments, especially with TNF-alpha(+)gamma delta T cells, TNF-alpha(+)gamma 9+delta T cells and IL17(+)CD4(-)CD8(-)gamma delta T cells subsets. Differential correlation patterns were also observed between serum cytokine levels and various gamma delta T cell compartments.ConclusionsA strong association exists between gamma delta T cell compartments and SLE pathogenesis, disease severity and response to therapy.