Co-stimulation of human decidual natural killer cells by interleukin-2 and stromal cells

At the late secretory phase of the menstrual cycle and in early pregnancy, the uterine mucosa is infiltrated by large numbers of natural killer (NK) cells with a distinctive phenotype (CD56bright CD16- CD3-) and large granular lymphocyte (LGL) morphology. Circulating CD56bright NK cells generally proliferate in the presence of interleukin-2 (IL-2), but it is clear that cofactors besides IL-2 are required for optimal response. In the bone marrow, this co-stimulating signal is provided by stromal cells. In the present study we observe that uterine CD56+ cells from early pregnancy decidua similarly proliferate vigorously when cultured with decidual stromal cells and a suboptimal dose of IL-2. This response is dependent on cell-cell contact, as no proliferation of decidual NK cells was observed when they were separated from stromal cells by a permeable cyclopore membrane. In addition, we have studied the expression of Bcl-2 by decidual CD56+ cells. Our results show that the microenvironment of the uterus is likely to have a significant influence on the proliferation and survival of uterine CD56+ cells.