T cell hyperactivation and
complement consumption are prominent features of the immunopathology of
systemic lupus erythematosus. Although complement activation is secondary to
autoantibodies that form
immune complexes (ICs), the trigger for alterations in human peripheral blood T cells is poorly understood. To study the impact (on T cells) of several types of preformed ICs and
terminal complement complex, also referred to as
C5b-9, we incubated these immune reactants with peripheral blood naive CD4(+) T cells as well as Jurkat cells and analyzed their effects on cellular behavior. We first assembled the
C5b-9 in situ on the membrane and observed its assembly primarily on a single site where it promoted aggregation of membrane rafts and recruitment of the CD3 signaling complex. However,
C5b-9 alone did not initiate proliferation or commencement of downstream signaling events associated with T cell activation. When T cells were treated with ICs together with nonlytic
C5b-9, changes associated with T cell activation by possible
antigen engagement then occurred.
T cell antigen receptor signaling
proteins, including ζ-chain, ZAP-70, Syk, Src, and Lck, were phosphorylated and organized in a synapse-like structure. The cytoskeleton formed
F-actin spindles and a distal pole complex, resulting in a bipolar distribution of phosphorylated
ezrin-
radixin-
moesin and
F-actin. Furthermore, ICs and nonlytic
C5b-9 induced T cell proliferation and IFN-γ production. These results raise the possibility that ICs and the nonlytic
C5b-9 modulate T cell-mediated responses in
systemic lupus erythematosus and other related chronic inflammatory disorders.