Co-stimulation of human decidual natural killer cells by interleukin-2 andstromal 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) c ells with a distinctive phenotype (CD56(bright) CD16(-) CD3(-)) and large g ranular lymphocyte (LGL) morphology, Circulating CD56(bright) NK cells gene rally 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 pre sent study we observe that uterine CD56(+) cells from early pregnancy decid ua similarly proliferate vigorously when cultured with decidual stromal cel ls and a suboptimal dose of IL-2. This response is dependent on cell-cell c ontact, as no proliferation of decidual NK cells was observed when they wer e separated from stromal cells by a permeable cyclopore membrane. Tn additi on, 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 si gnificant influence on the proliferation and survival of uterine CD56(+) ce lls.