Complement is engrained in the immunologist’s mind as quintessential part of innate immunity, vitally required for the detection and removal of invading pathogens or other dangerous entities. This current understanding of the complement system is rooted in two key paradigms: Complement operates as a serum (fluid phase) effector system and activation of complement is commonly connected with only a pro-inflammatory outcome – thus, increased or unwanted complement activation is thought to be also the cause of many autoimmune diseases. Work published in the last decade by several groups challenges this view: Complement is now clearly connected with the negati​ve regulation of – at minimum - human Th1 responses and in vivo significance has been demonstrated by identifying a defect in the complement-driven regulatory pathways in patients with the Th1-cell-mediated autoimmune disease rheumatoid arthritis and multiple sclerosis. Further, using pertinent patient groups and complement-deficient animals, it has been conclusively shown that “autocrine” T cell-derived, but not serum-derived, complement drives the induction and contraction of Th1 effector responses. Thus, complement has clearly a role in the negative regulation of adaptive immunity and this function is largely serum complement-independent. Also, upon a closer analysis of the modes of such local complement activation, we have found that complement activation is not – as always thought - confined to the extracellular space but can be activated intracellularly where it mediates specific intracellular signaling events connected with the cell’s nutrient and metabolism sensing machinery.

These paradigm shifts have significant implications for both basic science and clinical perspectives - particularly in regards to regulation of T cell effector responses and for the design of next generation therapeutics targeting complement in Th1-mediated diseases as they indicate that complement may be critical to many non-immune functions and to basic processes of the cell.

Claudia Kemper obtained her PhD from the Bernhard-Nocht-Institute for Tropical Medicine, University of Hamburg, Germany in 1998. She performed her postdoctoral fellowship in the laboratory of John Atkinson at Washington University School of Medicine in Saint Louis and became a faculty member of Washington University as an Instructor in Medicine and then Research Assistant Professor in 2004/2006. In 2008, Dr. Kemper joined the MRC Centre for Transplantation at King’s College London as a Senior Lecturer, became a Reader in 2012 and a Full Professor in 2015. Her research interest focuses on the role of innate signals, specifically those mediated by complement activation, in the regulation of T cell responses in normal immune homeostasis, in disease states such autoimmunity and cancer.

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