Agua-Doce, AnaCaridade, MartaOliveira, Vanessa GBergman, LisaLafaille, Maria CLafaille, Juan JDemengeot, JocelyneGraca, Luis2018-03-012018-03-012018-01-01Route of Antigen Presentation Can Determine the Selection of Foxp3-Dependent or Foxp3-Independent Dominant Immune Tolerance Ana Agua-Doce, Marta Caridade, Vanessa G. Oliveira, Lisa Bergman, Maria C. Lafaille, Juan J. Lafaille, Jocelyne Demengeot, Luis Graca The Journal of Immunology January 1, 2018, 200 (1) 101-109; DOI: 10.4049/jimmunol.1601886http://hdl.handle.net/10400.7/843This deposit is composed by a publication in which the IGC' authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and could only be accessed by two ways: either by requesting a legal copy to the author (the email contact present in this deposit) or by visiting the following link: http://www.jimmunol.org/content/200/1/101.long#ack-1This publication hasn't any creative commons license associated.It has been shown that dominant tolerance, namely in transplantation, requires Foxp3+regulatory T cells. Although most tolerance-inducing regimens rely on regulatory T cells, we found that induction of tolerance to proteins in aluminum hydroxide can be achieved in Foxp3-deficient mice using nondepleting anti-CD4 Abs. This type of tolerance is Ag specific, and tolerant mice retain immune competence to respond to unrelated Ags. We demonstrated with chicken OVA-specific TCR-transgenic mice that the same tolerizing protocol (CD4 blockade) and the same target Ag (OVA) achieves Foxp3-dependent transplantation tolerance to OVA-expressing skin grafts, but Foxp3-independent tolerance when the Ag is provided as OVA-aluminum hydroxide. In the latter case, we found that tolerance induction triggered recessive mechanisms leading to elimination of effector cells and, simultaneously, a dominant mechanism associated with the emergence of an anergic and regulatory CTLA-4+IL-2lowFoxp3-T cell population, where the tolerance state is IL-10 dependent. Such Foxp3-independent mechanisms can improve the efficacy of tolerance-inducing protocols.engAluminum HydroxideAnimalsAntibodiesAntigen PresentationCD4 AntigensCell DifferentiationCells, CulturedClonal Selection, Antigen-MediatedForkhead Transcription FactorsInterleukin-10Interleukin-2Lymphocyte ActivationMiceMice, KnockoutMice, TransgenicOvalbuminT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryImmune ToleranceSkin Transplantationjournal article10.4049/jimmunol.1601886