Glycodelin A triggers mitochondrial stress and apoptosis in T cells by a mechanism distinct and independent of TCR signaling

Glycodelin in reproductive endocrinology and hormone-related cancer

“…When a human T-cell leukaemia cell line and its derivative overexpressing antiapoptotic Bcl-2 were treated with glycodelin-A, the Bcl-2 overexpressing cells were resistant to mitochondrial membrane permeabilisation and apoptosis. This indicates that overexpression of Bcl-2 is sufficient to rescue these cells from glycodelin-A induced death (54). In addition to, the NK cell activity in the innate immune system, glycodelin also inhibits proliferation of several monocytic cell lines and induces apoptosis in these cell lines as well as in primary monocytes through caspaseindependent intrinsic mitochondrial pathway (64).…”

“…Glycodelin appears to desensitise T-cell receptor (TCR) signalling by its association with the tyrosine phosphatase receptor, CD45 (53). Other mechanisms may also be involved because glycodelin-A is inhibitory to T-cells upon phorbol ester and ionophore stimulation that bypass the TCR-proximal signalling events (54). The IC 50 for glycodelin-A activity on T-cells is around 200 nM (5.6 mg/l) (54).…”

“…This activity is caspase-dependent and is related to immunosuppressive activity (59). The effect is glycosylation dependent, which may explain some of the variable results (54,59,(61)(62)(63)(64). Specially, the terminal sialic acid residues and the size of the glycans appear important.…”

“…In peripheral blood T cells treated with glycodelin-A, mitochondrial depolarisation precedes the onset of DNA fragmentation in apoptosis (54). When a human T-cell leukaemia cell line and its derivative overexpressing antiapoptotic Bcl-2 were treated with glycodelin-A, the Bcl-2 overexpressing cells were resistant to mitochondrial membrane permeabilisation and apoptosis.…”

Implantation and Establishment of Pregnancy in Human and Nonhuman Primates

“…Galectin-1 is known as an inhibitor of T-cell proliferation and survival, and it promotes apoptosis of activated T cells in the decidua (Kopcow et al 2008). Glycodelin A inhibits T-cell activation through its ability to interact with the tyrosine phosphatase receptor CD45 on the T-cell surface (Rachmilewitz et al 2003; SundarRaj et al 2008). The uNK cell-mediated T-cell regulatory response is lost in patients who experience recurrent spontaneous abortions (RSA) due to extensive local inflammation (Fu et al 2013).…”