Redundant and Antagonistic Functions of Galectin-1, -3, and -8 in the Elicitation of T Cell Responses

Abstract

Galectins, a family of mammalian lectins, have emerged as key regulators of the immune response. We previously demonstrated that galectin (Gal)-8, from the tandem-repeat subgroup, exerts two well-defined effects on mouse naive peripheral CD4 T cells: Ag-specific costimulation and Ag-independent proliferation. These stimulatory signals on naive T cells have not been described for any other Gal. Therefore, we investigated whether Gal-1 and Gal-3, two prominent members of the Gal family, share the stimulatory effects exerted by Gal-8 on naive T cells. We found that Gal-1 costimulated Ag-specific T cell responses similarly to Gal-8, as evaluated in the DO11.10 TCROVA-transgenic mouse model, by acting simultaneously on APCs and target CD4 T cells. In contrast, Gal-3 failed to costimulate Ag-specific T cell responses; moreover, it antagonized both Gal-1 and Gal-8 signals. We observed that both Gal-1 and Gal-3 were unable to induce Ag-independent proliferation; however, when two Gal-1 molecules were covalently fused, the resulting chimeric protein efficiently promoted proliferation. This finding indicates that Gal-1 might eventually induce proliferation and, moreover, stresses the requirement of a tandem-repeat structure. Remarkably, a single dose of recombinant Gal-1 or Gal-8 administered together with a suboptimal Ag dose to DO11.10 mice strengthened weak responses in vivo. Taken together, these findings argue for the participation of Gals in the initiation of the immune response and allow the postulation of these lectins as enhancers of borderline Ag responses, thus representing potential adjuvants for vaccine formulations.

Galectin-3 Modulates Experimental Colitis

“…Gal-3 showed a suppression of IL-6, indicating a TH1-mediated suppression of inflammation in this model of colitis. These findings are in accordance with published data where gal-3 was capable to suppress T-cell responses [44] .…”

Trypanosoma cruzitrans-Sialidase Prevents Elicitation of Th1 Cell Response via Interleukin 10 and Downregulates Th1 Effector Cells

“…Recently, we showed that aTS but not iTS pushes isolated B cells to produce IL-17 through the activation of the CD45 pathway and sialyl pattern modification (47). T cells might also be modulated through a lectin pathway, as galectins activate T cells through CD45 (48), an effect that might be mimicked by the lectinlike activity of TSs. Unlike B or CD8 T cells, where a direct effect can be observed, thymocytes and CD4 T cells require an interaction with other cell type(s) to be affected by TSs.…”

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

“…In the immune system Gal-8 can play important roles in the homeostasis of T- Tribulatti et al, 2007;Norambuena et al, 2009;Tribulatti et al, 2009;Tribulatti et al, 2012) and B-cells (Tsai et al, 2011). Gal-8 expression in the thymus and its pro-apoptotic eff ects on CD4 high CD8 high thymocytes suggest a role in shaping the T cell repertoire (Tribulatti et al, 2007).…”