CD1d and invariant NKT cells at the human maternal–fetal interface

Abstract

Invariant CD1d-restricted natural killer T (iNKT) cells comprise a small, but significant, immunoregulatory T cell subset. Here, the presence of these cells and their CD1d ligand at the human maternal-fetal interface was investigated. Immunohistochemical staining of human decidua revealed the expression of CD1d on both villous and extravillous trophoblasts, the fetal cells that invade the maternal decidua. Decidual iNKT cells comprised 0.48% of the decidual CD3؉ T cell population, a frequency 10 times greater than that seen in peripheral blood. Interestingly, decidual CD4؉ iNKT cells exhibited a striking Th1-like bias (IFN-␥ production), whereas peripheral blood CD4؉ iNKT clones exhibited a Th2-like bias (IL-4 production). Moreover, compared to their peripheral blood counterparts, decidual iNKT clones were strongly polarized toward granulocyte͞macrophage colony-stimulating factor production. The demonstration of CD1d expression on fetal trophoblasts together with the differential pattern of cytokine expression by decidual iNKT cells suggests that maternal iNKT cell interactions with CD1d expressed on invading fetal cells may play an immunoregulatory role at the maternal-fetal interface.

NKT Cells at the Maternal-Fetal Interface

“…For the reasons discussed above, however, a variety of surrogate markers have been used to identify this population. Studies examining human decidual NKT cells are in general agreement that the classical NKT cell population is present at a frequency of approximately 0.5%, which is similar to what has been reported in the mouse (Boyson et al 2002;Ito et al 2000;Tsuda et al 2001). Similarly, in both humans and mice, classical NKT cells appear to be highly activated and exhibit a Th1-like bias towards production of IFN-γ (Boyson et al 2002;Ito et al 2000).…”

“…NKT cells have been described in both the mouse and human decidua (Boyson et al 2002;Ito et al 2000;Tsuda et al 2001). For the reasons discussed above, however, a variety of surrogate markers have been used to identify this population.…”

“…Recently, we and others reported the presence of NKT cells in the human and mouse decidua (Boyson et al 2002;Ito et al 2000;Tsuda et al 2001). This small T cell subset has been demonstrated to modulate both innate and adaptive immune responses (Kronenberg and Gapin 2002) and, although the role of these cells in the decidua is unknown, experiments in the mouse have demonstrated that NKT stimulation dramatically impacts pregnancy, resulting in rapid pregnancy loss (Ito et al 2000).…”

Immune cells in the placental bed

“…The relative proportion of both iNKT and non-iNKT is greatly enriched in decidua compared to peripheral blood of the same patients (Tsuda et al, 2001;Boyson et al, 2002;Uemura et al, 2008).…”

CD56brightCD25+ NK cells are preferentially recruited to the maternal/fetal interface in early human pregnancy

“…At the maternal/fetal interface, dNK cells are in close contact with invading trophoblasts, which lack expression of classical HLA-A and -B antigens but selectively express HLA-C and the non-classical HLA-E, -G and CD1d molecules. 14,15 This has led to the theory that trophoblasts interact with NK cells via their MHC antigens. 16 In addition, a recent discovery has shown that dNK cells play a critical role in modulating trophoblast invasion and vascular remodeling.…”