Cedeno-Laurent F, Watanabe R, Teague JE et al.Galectin-1 inhibits the viability, proliferation, and Th1 cytokine production of nonmalignant T cells in patients with leukemic cutaneous T-cell lymphoma. Blood 119:3534-3538
Tumor-derived galectin-1 (Gal-1), a β-galactoside-binding S-type lectin, has been shown to encourage T-cell death and promote T cell-mediated tumor immune escape. In this report, we show that patients with leukemic cutaneous T-cell lymphomas, known to have limited complexity of their T-cell repertoires, have a predominant T helper type-2 (Th2) cytokine profile and significantly elevated plasma levels of Gal-1 compared with healthy controls. Circulating clonal malignant T cells were a major source of Gal-1. The conditioned supernatant of cultured malignant T cells induced a β-galactoside-dependent inhibition of normal T-cell proliferation and a Th2 skewing of cytokine production. These data implicate Gal-1 in development of the Th2 phenotype in patients with advanced-stage cutaneous T-cell lymphoma and highlight the Gal-1-Gal-1 ligand axis as a potential therapeutic target for enhancing antitumor immune responses.
"Galectins, a family of S-type lectins found in a large scale of species, are characterized by two features: a specific affinity for β-galactoside and a conserved specific sequence motif called carbohydrate recognition domain (CRD)
. To date, 15 mammalian galectins (galectin-1 to -15) have been cloned and functionally characterized
, revealing various roles in apoptosis
, cell adhesion
, cell proliferation
, cytokine secretion
 and immune responses
. After the discovery of the first nematode tandem repeat type galectin in Caenorhabditis elegans (C. "
[Show abstract][Hide abstract] ABSTRACT: Monocytes and T cells are two major subpopulations of peripheral blood mononuclear cells (PBMC) and play an essential role in the innate and adaptive immune systems. Different members of the galectin family show multiple and distinct regulatory effects on different cell types. Previous studies have demonstrated that the galectin from Haemonchus contortus (Hco-gal-m) performed immunomodulatory effects on goat PBMC, however, which subpopulation of PBMC is the primary target of Hco-gal-m and whether the immune modulations share the same mechanism remain unclear.
In this study, the developmental expression of Hco-gal-m was analyzed by RT-PCR and Western blot analysis. The distribution of Hco-gal-m in adult worm was detected by an immunohistochemical test. The binding activity of the recombinant Hco-gal-m (rHco-gal-m) on goat monocytes and T cells were assessed by flow cytometry. The immunomodulatory effects of Hco-gal-m on cytokine secretion, cell activation and apoptosis were observed by co-incubation of rHco-gal-m with goat monocytes and T cells.
Hco-gal-m was expressed in L4 as well as adult worms and predominantly localized at the internal surface of the worm guts. rHco-gal-m could bind to both monocytes and T cells. The engagement of rHco-gal-m decreased the production of IL-6, IL-10 and TNF-α in T cells, however, it significantly increased the secretion of IL-10 in monocytes. After rHco-gal-m exposure, the expression of MHC-II on monocytes and that of CD25 on T cells were restricted. Consequently, T cell proliferations were potently inhibited by rHco-gal-m. In addition, rHco-gal-m induced apoptosis in T cells, but not significantly in monocytes.
Our results indicated that rHco-gal-m modulated goat monocytes and T cell function in different patterns.
[Show abstract][Hide abstract] ABSTRACT: Mechanisms accounting for the protection of the fetal semi-allograft from maternal immune cells remain incompletely understood. In previous studies, we showed that galectin-1 (Gal1), an immunoregulatory glycan-binding protein, hierarchically triggers a cascade of tolerogenic events at the mouse fetomaternal interface. Here, we show that Gal1 confers immune privilege to human trophoblast cells through the modulation of a number of regulatory mechanisms. Gal1 was mainly expressed in invasive extravillous trophoblast cells of human first trimester and term placenta in direct contact with maternal tissue. Expression of Gal1 by the human trophoblast cell line JEG-3 was primarily controlled by progesterone and pro-inflammatory cytokines and impaired T-cell responses by limiting T cell viability, suppressing the secretion of Th1-type cytokines and favoring the expansion of CD4(+)CD25(+)FoxP3(+) regulatory T (T(reg)) cells. Targeted inhibition of Gal1 expression through antibody (Ab)-mediated blockade, addition of the specific disaccharide lactose or retroviral-mediated siRNA strategies prevented these immunoregulatory effects. Consistent with a homeostatic role of endogenous Gal1, patients with recurrent pregnancy loss showed considerably lower levels of circulating Gal1 and had higher frequency of anti-Gal1 auto-Abs in their sera compared with fertile women. Thus, endogenous Gal1 confers immune privilege to human trophoblast cells by triggering a broad tolerogenic program with potential implications in threatened pregnancies.
[Show abstract][Hide abstract] ABSTRACT: Kaposi’s sarcoma (KS), a multifocal vascular neoplasm linked to human herpesvirus-8 (HHV-8/KS-associated herpesvirus [KSHV])
infection, is the most common AIDS-associated malignancy. Clinical management of KS has proven to be challenging because of
its prevalence in immunosuppressed patients and its unique vascular and inflammatory nature that is sustained by viral and
host-derived paracrine-acting factors primarily released under hypoxic conditions. We show that interactions between the regulatory
lectin galectin-1 (Gal-1) and specific target N-glycans link tumor hypoxia to neovascularization as part of the pathogenesis
of KS. Expression of Gal-1 is found to be a hallmark of human KS but not other vascular pathologies and is directly induced
by both KSHV and hypoxia. Interestingly, hypoxia induced Gal-1 through mechanisms that are independent of hypoxia-inducible
factor (HIF) 1α and HIF-2α but involved reactive oxygen species–dependent activation of the transcription factor nuclear factor
κB. Targeted disruption of Gal-1–N-glycan interactions eliminated hypoxia-driven angiogenesis and suppressed tumorigenesis
in vivo. Therapeutic administration of a Gal-1–specific neutralizing mAb attenuated abnormal angiogenesis and promoted tumor
regression in mice bearing established KS tumors. Given the active search for HIF-independent mechanisms that serve to couple
tumor hypoxia to pathological angiogenesis, our findings provide novel opportunities not only for treating KS patients but
also for understanding and managing a variety of solid tumors.
Journal of Experimental Medicine 10/2012; 209(11):1985-2000. DOI:10.1084/jem.20111665 · 12.52 Impact Factor
Mirjana Nacka-Aleksić, Ivan Pilipović, Zorica Stojić-Vukanić, Duško Kosec, Biljana Bufan, Ivana Vujnović, Nevena Arsenović-Ranin, Mirjana Dimitrijević, Gordana Leposavić
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.