Complement modulation of T cell immune responses during homeostasis and disease

• Published in: Journal of leukocyte biology Vol. 96; no. 5; pp. 745 - 756
• Main Authors: Clarke, Elizabeth V., Tenner, Andrea J.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.11.2014
• Subjects: Animals; C1q; C5a; CD46; CD55 Antigens - genetics; CD55 Antigens - immunology; CD55 Antigens - metabolism; Complement C1q - genetics; Complement C1q - immunology; Complement C1q - metabolism; Complement C3 - genetics; Complement C3 - immunology; Complement C3 - metabolism; Complement C5a - genetics; Complement C5a - immunology; Complement C5a - metabolism; Complement System Proteins - genetics; Complement System Proteins - immunology; Complement System Proteins - metabolism; DAF; Homeostasis - genetics; Homeostasis - immunology; Humans; Immunomodulation; Membrane Cofactor Protein - genetics; Membrane Cofactor Protein - immunology; Membrane Cofactor Protein - metabolism; Reviews; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; C3; DAF; C1q; CD46; C5a
• DOI: 10.1189/jlb.3MR0214-109R
• ISSN: 0741-5400

Review on the influence of complement proteins, activation fragments, and regulatory receptors on T cell function, noting differences between humans and mice. The complement system is an ancient and critical effector mechanism of the innate immune system as it senses, kills, and clears infectious and/or dangerous particles and alerts the immune system to the presence of the infection and/or danger. Interestingly, an increasing number of reports have demonstrated a clear role for complement in the adaptive immune system as well. Of note, a number of recent studies have identified previously unknown roles for complement proteins, receptors, and regulators in T cell function. Here, we will review recent data demonstrating the influence of complement proteins C1q, C3b/iC3b, C3a (and C3aR), and C5a (and C5aR) and complement regulators DAF (CD55) and CD46 (MCP) on T cell function during homeostasis and disease. Although new concepts are beginning to emerge in the field of complement regulation of T cell function, future experiments should focus on whether complement is interacting directly with the T cell or is having an indirect effect on T cell function via APCs, the cytokine milieu, or downstream complement activation products. Importantly, the identification of the pivotal molecular pathways in the human systems will be beneficial in the translation of concepts derived from model systems to therapeutic targeting for treatment of human disorders.