Leishmania-Infected MHC Class IIhigh Dendritic Cells Polarize CD4(+) T Cells toward a Nonprotective T-bet(+) IFN-gamma(+) IL-10(+) Phenotype

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Mariana Resende (Author) Other; Diana Moreira (Author) Other; Jorge Augusto (Author) Other; Joana Cunha (Author) Other; Bruno Neves (Author) Other; Maria Teresa Cruz (Author) Other; Jerome Estaquier (Author) Other; Anabela Cordeiro da Silva (Author) FFUP; Ricardo Silvestre (Author) Other

Journal

Title: Journal of Immunology

Vol. 191

Pages: 262-273

ISSN: 0022-1767

Publisher: American Association of Immunologists

Indexing

ISI Web of Knowledge - 19 Citations

Scopus - 26 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-006-9Q9

DOI: 10.4049/jimmunol.1203518

Abstract (EN): A differential behavior among infected and bystander dendritic cells (DCs) has been explored in different infection models. We have analyzed both populations sorted on contact with visceral Leishmania infantum on a susceptible mice model evaluating the subsequent repercussions on adaptive immune response. Our results demonstrate a clear dichotomy between the immunomodulatory abilities of bystander and infected DCs. The bystander population presents increased levels of IL-12p40 and costimulatory molecules being capable to induce CD4(+) T cell activation with immune protective capabilities. In contrast, infected DCs, which express lower costimulatory molecules and higher levels of IL-10, promote the development of Leishmania Ag-specific, non-protective T-bet(+)IFN-gamma+IL-10(+) CD4(+) T cells with an effector phenotype. This specific polarization was found to be dependent on IL-12p70. Splenic infected DCs recovered from chronic infected animals are similarly capable to polarize ex vivo syngeneic naive CD4(+) T cells toward a T-bet(+)IFN-gamma+IL-10(+) phenotype. Further analysis revealed that only MHC class IIhigh-infected DCs were responsible for this polarization. The adoptive transfer of such polarized CD4(+) T cells facilitates visceral leishmaniasis in BALB/c mice in a clear contrast with their counterpart generated with bystander DCs that significantly potentiate protection. Further, we demonstrated that CD4(+) T cells primed by infected DCs in an IL-10 free system, thus deprived of T-bet(+)IFN-gamma+IL-10(+) population, restore the immune response and reduce parasite load, supporting a deleterious role of IFN-gamma+IL-10(+) T cells in the maintenance of infection. Overall, our results highlight novel subversion mechanisms by which nonprotective T-bet(+)IFN-gamma+IL-10(+) T cells are associated with chronicity and prolonged parasite persistence.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12