Peripheral Blood TIM-3 Positive NK and CD8+ T Cells throughout Pregnancy: TIM-3/Galectin-9 Interaction and Its Possible Role during Pregnancy

Abstract

ProblemThe T-cell immunoglobulin and mucin domain (TIM) family is a relatively newly described group of molecules with a conserved structure and important immunological functions. Identification of Galectin-9 as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important negative regulator of Th1 immunity and tolerance induction. Data about the TIM-3/Gal-9 pathway in the pathogenesis of human diseases is emerging, but their possible role during human pregnancy is not precisely known. The aim of our study was to investigate the number, phenotype and functional activity of TIM-3+ peripheral blood mononuclear cells during healthy human pregnancy.Methods of Study57 healthy pregnant women [first trimester (n = 16); second trimester (n = 19); third trimester (n = 22)] and 30 non-pregnant controls were enrolled in the study. We measured the surface expression of TIM-3 by cytotoxic T cells, NK cells and NK cell subsets as well as Galectin-9 expression by regulatory T cells by flow cytometry. We analyzed the cytokine production and cytotoxicity of TIM3+ and TIM3- CD8 T and NK cells obtained from non-pregnant and healthy pregnant women at different stages of pregnancy by flow cytometry. Serum Galectin-9 levels were measured by ELISA.ResultsOur results show that the numbers of peripheral NK and cytotoxic T cells and their TIM-3 expression do not change between the first, second and third trimesters of pregnancy. Compared to non-pregnant individuals, regulatory T cells show higher level of Galectin-9 expression as pregnancy proceeds, which is in line with the level of Galectin-9 in the patients sera. Cytotoxic T cells, NK cells and NK cell subsets expressing TIM-3 molecule show altered cytokine production and cytotoxicity during pregnancy compared to non-pregnant individuals.ConclusionOur results indicate that Galectin-9 expressing regulatory T cells, TIM-3+ cytotoxic T cells and NK cells could play an important role in the maintenance of healthy pregnancy.

Galectin-9 modulates immunity by promoting Th2/M2 differentiation and impacts survival in patients with metastatic melanoma

“…T-cell immunoglobulin and mucin-domain containing-3 (Tim3) is the most well characterized binding partner of galectin-9, and their interaction was shown to negatively regulate Th1 type responses through apoptosis of activated CD4+ cells (13, 14). Remarkably, galectin-9/Tim3 regulation at the feto-maternal interface seems to be critical for the development and maintenance of healthy pregnancies (15, 16). Many similarities exist between tumor and trophoblastic development and regulation in promoting immune tolerance (17, 18).…”

Human galectin‐9 on the porcine cells affects the cytotoxic activity of M1‐differentiated THP‐1 cells through inducing a shift in M2‐differentiated THP‐1 cells

“…14 Functional studies of Gal-9 with Th1, Th2, Th17, Treg, and NK cells have been carried out extensively. 15,16 However, fewer evidences with THP-1/differentiated THP-1 such as myeloid lineage immune cells compared to lymphoid lineage immune cells have been shown. Many recent studies have shown that TIM-3 is expressed in myeloid lineage immune cells, notably antigen-presenting cells (APSs).…”

Tim-3 Expression by Peripheral Natural Killer Cells and Natural Killer T Cells Increases in Patients with Lung Cancer - Reduction after Surgical Resection

“…In recent years, studies have demonstrated that T cell immunoglobulin and mucin domain 3 (Tim-3) is closely associated with dysregulation of innate immune cells, including macrophages/monocytes (Yang et al, 2013), dendritic cells (Chiba et al, 2012), and NK cells (Gleason et al, 2012). Abnormal expression of Tim-3 on these innate immune cells was found to be involved in the progression of many clinical diseases (Wu et al, 2012;Anderson et al, 2012;da Silva et al, 2014;Meggyes et al, 2014). However, it was not reported the relationship between Tim-3 expression on NK cells and NKT cells and lung cancer.…”