title: Down-regulation of macrophage immune activity by natural CD8+ regulatory T cells.
abstract: To evaluate the influence of natural regulatory CD8+ T cells on macrophages we investigated in vitro production of cytokines, reactive oxygen intermediates (ROIs) and expression of CD80 surface costimulatory molecules by macrophages (MF) of wild type (WT) B10PL and syngeneic knock-out (KO) strains, TCRalpha-/-, beta2m-/- and CD1d-/- mice. MF of TCR alpha-/- (CD4- and CD8-) and beta2m-/- (CD8-) animals produced higher levels ofTNF-a, IL-6, IL-12 and ROIs and showed increased expression of CD80 costimulatory molecules in comparison to MF of WT or CD1d-/- (NKT-) mice. When MF of these strains were conjugated with TNP hapten and injected i.v. into WT mice to test either induction of contact sensitivity (CS) or tolerance, only TNP-MF of TCRalpha-/- and beta2m-/- animals induced a significant CS reaction, while cells of WT and CD1d-/- strains were tolerogenic. MF of the tested strains can be classified functionally as resembling either proinflammatory (TCRalpha-/- and beta2m-/-mice) or immunosuppressive (WT and CD1d-/-) phenotypes. We suggest the presence of an in vivo regulatory loop in which innate CD8+ Treg cells control the transition between MF phenotypes and thus adjust the magnitude of the inflammatory response to strictly local requirements.
authors.affiliation: Department of Immunology, Jagiellonian University Medical College, Czysta 18, 31-121 Kraków, Poland. mmbrynia@cyf-kr.edu.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bryniarski
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
authors.forename: Maria
authors.initials: M
authors.lastname: Ptak
authors.forename: Emilia
authors.initials: E
authors.lastname: Sikora
authors.forename: Monika
authors.initials: M
authors.lastname: Majewska-Szczepanik
authors.forename: Włodzimierz
authors.initials: W
authors.lastname: Ptak
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D017353:Gene Deletion; D007694:Killer Cells, Natural; D017737:Macrophages, Peritoneal / Q000502:physiology*; D008297:Male; D051379:Mice; D017382:Reactive Oxygen Species
chemical_list: D017382:Reactive Oxygen Species