ArtinM Mediates Murine T Cell Activation and Induces Cell Death in Jurkat Human Leukemic T Cells

Author(s)

da Silva, Thiago Aparecido ; Martins Oliveira-Brito, Patricia Kellen ; Goncalves, Thiago Eleuterio ; Vendruscolo, Patricia Edivania ; Roque-Barreira, Maria Cristina

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 18, n. 7, p. 21-pg., 2017-07-01.

Abstract

The recognition of cell surface glycans by lectins may be critical for the innate and adaptive immune responses. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, activates antigen-presenting cells by recognizing TLR2 N-glycans and induces Th1 immunity. We recently demonstrated that ArtinM stimulated CD4(+) T cells to produce proinflammatory cytokines. Here, we further studied the effects of ArtinM on adaptive immune cells. We showed that ArtinM activates murine CD4(+) and CD8(+) T cells, augmenting their positivity for CD25, CD69, and CD95 and showed higher interleukin (IL)-2 and interferon (IFN)-gamma production. The CD4(+) T cells exhibited increased T-bet expression in response to ArtinM, and IL-2 production by CD4(+) and CD8(+) T cells depended on the recognition of CD3 epsilon gamma-chain glycans by ArtinM. The ArtinM effect on aberrantly-glycosylated neoplastic lymphocytes was studied in Jurkat T cells, in which ArtinM induced IL-2, IFN-gamma, and IL-1 beta production, but decreased cell viability and growth. A higher frequency of AnnexinV -and propidium iodide-stained cells demonstrated the induction of Jurkat T cells apoptosis by ArtinM, and this apoptotic response was reduced by caspases and protein tyrosine kinase inhibitors. The ArtinM effects on murine T cells corroborated with the immunomodulatory property of lectin, whereas the promotion of Jurkat T cells apoptosis may reflect a potential applicability of ArtinM in novel strategies for treating lymphocytic leukemia. (AU)

• FAPESP's process: 16/23112-7 - The immunomodulatory activity of ArtinM on the course of Cryptococcus gattii infection
• Grantee: Patrícia Kellen Martins Oliveira Brito
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/10446-4 - Mechanisms of immunomodulation by ArtinM: basis for the development of new anti-fungal therapy
• Grantee: Maria Cristina Roque Antunes Barreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 06/60642-2 - Lectins: biological effects and pharmaceutical applications
• Grantee: Maria Cristina Roque Antunes Barreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/04088-0 - Lectin from pathogens
• Grantee: Maria Cristina Roque Antunes Barreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/09611-0 - Effect of lectin ArtinM on murine CD4+ T and CD8+ T cells
• Grantee: Thiago Aparecido da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/16003-1 - Effect of adoptive transfer of spleen cells or CD4+ T cells stimulated with ArtinM during infection with Paracoccidioides brasiliensis
• Grantee: Thiago Eleutério Gonçalves
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/04877-2 - Design of new therapeutic strategies, based on the carbohydrate recognition, against cryptococcosis
• Grantee: Thiago Aparecido da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral