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Route of Antigen Presentation Can Determine the Selection of Foxp3-Dependent or Foxp3-Independent Dominant Immune Tolerance
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Advisor(s)
Abstract(s)
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.
Description
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
This publication hasn't any creative commons license associated.
This publication hasn't any creative commons license associated.
Keywords
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
Citation
Route 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.1601886
Publisher
American Association of Immunologists