Janeway's conceptualization of the 'adjuvant effect' as being due to the influence of the innate immune system on T cell immunity led to an intense study of how pathogens are recognized by DCs and other professional antigen-presenting cells (APCs). Much of the focus has been directed at the growing family of TLRs that recognize a wide range of bacterial structures. Not unexpectedly, the complement system also seems to participate in T cell immunity through its property of marking antigens as foreign and recognition by specific receptors. Early studies examining the function of complement in T cell priming suggested that its involvement was more important in B cell immunity. C3-deficient mice immunized with noninfectious antigens such as haptenated keyhole limpet hemocyanin or bacteriophage developed apparently normal T cell responses, yet humoral responses were impaired.
In summary, it is becoming increasingly clear that the complement system participates in regulation of T cells by multiple mechanisms such as direct opsonization of foreign antigens by APCs and by modulating cytokine release. Stimulation of the chemoattractant receptors C3aR and C5aR by products of complement activation also alters T cell responses by mechanisms that remain unclear. Finally, the CD46 receptor that is widely expressed on human cells appears to be involved in regulation of the activity of T cells via both cytokine modulation and differentiation of regulatory T cells.
1. Janeway C A. (1989). Approaching the asymptote. Evolution and revolution in immunology. 54, 1-13.
2. Carroll M C. (2004). The complement system in regulation of adaptive immunity. Nature immunology, 5(10), 981-986.
3. Ricklin D, et al. (2010). Complement: a key system for immune surveillance and homeostasis. Nature immunology, 11(9), 785-797.