T-cell stimulation and regulation: with complements from CD46.
Crosslinking of CD46 and CD3 on naïve human CD4+ T-lymphocytes induces interleukin-10 secretion and granzyme B expression. These highly proliferative T-regulatory type 1-like T-regulatory T-cells (Tregs) can suppress an immune response. We propose that this process is important in the prevention of chronic inflammation such as at epithelial borders and in deactivation of a successful immune response. Relative to the latter, once a complement-fixing polyclonal antibody response has been mounted, in most cases, the pathogen will be rapidly destroyed. At this time, the C3b/C4b-bearing immune complexes could initiate the deactivation arm of an immune response by shutting down immunocompetent cells through CD46-generated T-cells. Herein, we review this pathway for the induction of Tregs, focusing on a role for the complement system and especially signaling through CD46 on human T-cells.
Kemper
Claudia
C
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Verbsky
James W
JW
Price
Jeffrey D
JD
Atkinson
John P
JP
D000595:Amino Acid Sequence; D000818:Animals; D003165:Complement System Proteins / Q000378:metabolism*; D053804:Granzymes; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D051916:Membrane Cofactor Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D008969:Molecular Sequence Data; D012697:Serine Endopeptidases / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C497857:CD46 protein, human; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D016753:Interleukin-10; D003165:Complement System Proteins; C509213:GZMB protein, human; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases