title: Mycobacteria-primed macrophages and dendritic cells induce an up-regulation of complement C5a anaphylatoxin receptor (CD88) in CD3+ murine T cells.
abstract: Complement C5a anaphylatoxin is a potent activator of macrophages, neutrophils, and dendritic cells (DC) and binds the C5a receptor (C5a-R; CD88). Although C5a is chemotactic for T cells, expression of C5a-R on murine T cells has been disputed. We report here that naïve, Con A-activated, and cytokine (IL-12, IL-18)-stimulated murine CD3+ T cells from three strains of mice [C57Bl/6, B10.nSn (C5+/+), B10.on (C5-/-)] lacked C5a-R, as evaluated by immunophenotyping with an anti-C5a-R mAb. Ligation of CD3 induced a modest up-regulation with 3% of CD3+ T cells expressing cell surface C5a-R. T cells primed by APC differentiate into effector T cells. Activation of mycobacteria [bacillus Calmette-Guerin (BCG)]-sensitized T cells through MHC II and TCR interactions via BCG-infected macrophages enhanced the expression of C5a-R with approximately 14% of CD3+ T cells positive for C5a-R. Comparable expression was found in C5+/+ as well as C5-/- strains of mice (14% and 15%, respectively). Furthermore, anti-CD3-activated T cells were primed by BCG-infected DC, and a larger proportion of the primed T cells expressed C5a-R (30-40%). Finally, mice infected with BCG showed significant numbers of CD3+ T cells expressing C5a-R in the spleens during infection. As APC, such as macrophages and DC, can secrete C5 and cleave C5 to C5a and C5b through a peptidase, we suggest that macrophage and DC-T cell interactions can up-regulate C5a-R on T cells through MHC II-TCR and provide a C5a peptide for additional local activation of T cells via C5a-R.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center, MSB 2.200, 6431 Fannin, Houston, TX 77030, USA.
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Connelly
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Moulton
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Smith
authors.forename: Devin R
authors.initials: DR
authors.lastname: Lindsey
authors.forename: Meenal
authors.initials: M
authors.lastname: Sinha
authors.forename: Rick A
authors.initials: RA
authors.lastname: Wetsel
authors.forename: Chinnaswamy
authors.initials: C
authors.lastname: Jagannath
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D017252:CD3 Complex / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009161:Mycobacterium / Q000502:physiology*; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000378:metabolism*; D012685:Sepharose / Q000031:analogs & derivatives / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D017252:CD3 Complex; D044087:Receptor, Anaphylatoxin C5a; C028326:concanavalin A-sepharose; D012685:Sepharose