title: 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 TCR(OVA)-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.
authors.affiliation: Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas, B1650WGA San Martín, Buenos Aires, Argentina. virginiatribu@gmail.com
authors.forename: María Virginia
authors.initials: MV
authors.lastname: Tribulatti
authors.forename: María Gabriela
authors.initials: MG
authors.lastname: Figini
authors.forename: Julieta
authors.initials: J
authors.lastname: Carabelli
authors.forename: Valentina
authors.initials: V
authors.lastname: Cattaneo
authors.forename: Oscar
authors.initials: O
authors.lastname: Campetella
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004347:Drug Interactions; D037483:Galectin 1 / Q000235:genetics / Q000502:physiology*; D037502:Galectin 3 / Q000235:genetics / Q000502:physiology*; D037161:Galectins / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D020080:Tandem Repeat Sequences
chemical_list: D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; C485095:Lgals3 protein, mouse; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C526554:galectin-8, mouse; D010047:Ovalbumin