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

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)-γ 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 CD3εγ-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-γ, and IL-1β 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.

Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

“…Previous study reported that ArtinM induces polyclonal B cell activation, followed by high immunoglobulins secretion, in a manner that is T cell-independent [ 47 ]. Recently, our group demonstrated that ArtinM induces the activation of murine CD4 + and CD8 + T cells [ 13 , 14 , 48 ], whereas in the present work we found that ArtinM treated mice exhibit a significant increase in the frequency of CD4 + T and B cells in the spleen ( Fig 8 ). The ability of ArtinM to elicit the activation of adaptive immune cells [ 13 , 14 , 48 ] seems to be related to augmented production of immunoglobulins and the resultant alteration in the serum proteins.…”

“…Recently, our group demonstrated that ArtinM induces the activation of murine CD4 + and CD8 + T cells [ 13 , 14 , 48 ], whereas in the present work we found that ArtinM treated mice exhibit a significant increase in the frequency of CD4 + T and B cells in the spleen ( Fig 8 ). The ability of ArtinM to elicit the activation of adaptive immune cells [ 13 , 14 , 48 ] seems to be related to augmented production of immunoglobulins and the resultant alteration in the serum proteins. The augmented levels of CK-MB that follow the ArtinM administration at high doses may be associated with the presence of mononuclear cells and high levels of MPO in the heart.…”

The lectin ArtinM activates RBL-2H3 mast cells without inducing degranulation

“…ArtinM also has a direct effect on CD4+ T cells, stimulating IL-17 production [46]. Activation of murine CD4⁺ and CD8⁺ T cells by ArtinM result in increased release of IL-2 and IFN-γ [47]. Furthermore, ArtinM activates murine B cells, increasing IL-17 and IL-12p40 production [48].…”

“…Expression of PCNA and p63 are both important for proliferation and differentiation of the stratified epithelium [6]. In contrast, exposure to high concentrations of ArtinM induced apoptosis in Jurkat T cells [47].…”

The Response of IL-17-Producing B Cells to ArtinM Is Independent of Its Interaction with TLR2 and CD14

“…These authors described that B cells are the principal source of IL-17 after infection with T. cruzi , and that direct exposure to T. cruzi , or to the trans-sialidase enzyme from this parasite, is responsible for the induction of IL-17 production in B cells [ 14 , 15 ]. Our group has been investigating the direct effect of ArtinM on murine T cells in order to understand the mechanisms involved in the immunomodulatory activity triggered by ArtinM [ 21 , 22 , 30 , 31 ], and the capacity of ArtinM to induce IL-17 production in spleen cells and CD4 + T cells was recently reported [ 21 ]. Interestingly, we found reduced levels of IL-17 induced by ArtinM in spleen cells after B-cell depletion [ 21 ], and the polyclonal activation of B cells induced by ArtinM was verified in naïve mice that received ArtinM at various doses [ 32 ].…”