Document details

Route of Antigen Presentation Can Determine the Selection of Foxp3-Dependent or Foxp3-Independent Dominant Immune Tolerance

Author(s): Agua-Doce, Ana ; Caridade, Marta ; Oliveira, Vanessa G ; Bergman, Lisa ; Lafaille, Maria C ; Lafaille, Juan J ; Demengeot, Jocelyne ; Graca, Luis

Date: 2018

Persistent ID: http://hdl.handle.net/10400.7/843

Origin: ARCA - Access to Research and Communication Annals

Project/scholarship: info:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-ICT%2F0034%2F2013/PT;

Subject(s): Aluminum Hydroxide; Animals; Antibodies; Antigen Presentation; CD4 Antigens; Cell Differentiation; Cells, Cultured; Clonal Selection, Antigen-Mediated; Forkhead Transcription Factors; Interleukin-10; Interleukin-2; Lymphocyte Activation; Mice; Mice, Knockout; Mice, Transgenic; Ovalbumin; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Immune Tolerance; Skin Transplantation


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This 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-1

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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.

Fundacao para a Ciencia e Tecnologia grant: (HMSP-ICT/0034/2013); FEDER through POR Lisboa 2020–Programa Operacional Regional de Lisboa grant: (LISBOA-01-0145-FEDER-007391).

Document Type Journal article
Language English
Contributor(s) ARCA
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