TNF and granulomatosis with polyangiitis: In ANCA-associated vasculitis, CD28 was found to be downregulated on circulating and lesional CD4+ T- cells [46] and CD4+CD28- T-cells have been described as the major source of pro-inflammatory cytokines (particularly IFN-γ and TNF-α) in Wegener’s Granulomatosis [47].