Complement regulation of T cell immunity

Abstract

Results of studies published since 2002 reveal that T cells and antigen-presenting cells (APCs) produce complement proteins. The immune cell-derived, alternative pathway complement components activate spontaneously, yielding local, but not systemic, production of C3a and C5a. These anaphylatoxins to bind their respective G-protein coupled receptors, C3aR and C5aR, expressed on both partners. The resultant complement-induced T cell and APC activation drives T cell differentiation, expansion and survival. Complement deficiency or blockade attenuates T cell mediated autoimmunity and delays allograft rejection in mice. Increasing complement activation, achieved by genetic removal of the complement regulatory protein decay accelerating factor (DAF), enhances murine T cell immunity and accelerates allograft rejection. The findings support the need for design and testing of complement inhibitors in humans.

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

“…Accumulating evidence shows that the complement system plays a very important role in the regulation of T cell immunity (16,17,46), particularly in the regulation of primary CD8 + T cell responses in certain models of bacterial and viral infection (19,29,35,39). The present study was undertaken to determine the role of C3 in regulating CD8 + T cell contraction and memory induction.…”

“…A large body of evidence originally established the role of the complement system in the innate immune response against pathogens through its functions of opsonization, lysis, and anaphylatoxin activity (13)(14)(15). Subsequent research revealed that the complement system is involved in the induction and regulation of B cell-and T cell-mediated responses (13,(15)(16)(17)(18). Complement activation regulates CD8 + T cell priming and proliferation in naturally occurring viral infections and in models of transplantation (16,19,20).…”

Production of complement components by cells of the immune system

“…moDCs have been shown to produce various functional complement components, and they additionally express complement regulators CD46, CD55 and CD59 [80,88]. Importantly, transient down-regulation of CD55 during APC-T cell interaction has been identified as an important mechanism to allow local complement activation [89]. Other membrane-bound proteins found on the moDCs are several complement receptors, namely CR1, CR3, CR4, CRIg, C3aR and C5aR1 [87,88].…”

Immunological Challenges and Therapies in Xenotransplantation

“…This approach represents an elegant strategy for down-regulating local complement activation on the xenograft while preserving systemic complement activity as a first line of defense. The expression of hCRP by the xenograft cell sur-face may have a beneficial role on T-cell immunity too because molecules such as hCD55 can negatively modulate T-cell expansion and function (Heeger et al 2005;Kwan et al 2012). Judging from the data obtained so far, however, pig xenografts expressing CRPs are not protected from the overwhelming complement activation occurring in AHXR, even if CRPs are expressed on a GalT-KO background.…”

“…Taken together, these findings show the important role of the aGal epitope in the production of proinflammatory cytokines by human blood cells, as well as the central role of complement in mediating human immune effector functions and porcine cell activation. Recent evidence of a complement-induced T-cell and APC activation should also be borne in mind and warrants further analysis (Kwan et al 2012).…”