UTERINE NATURAL-KILLER-CELLS DO NOT REQUIRE INTERLEUKIN-2 FOR THEIR DIFFERENTIATION OR MATURATION

PROBLEM: Natural Killer lymphocytes (NK cells) from the pregnant uteru s and from other tissues in pregnant and nonpregnant mammals can be st imulated by interleukin-2 (IL-2) during culture to become Lymphokine A ctivated Killer (LAK) cells, The susceptibility of cultured trophoblas t cells to lysis by LAK cells raises the enigma of why uterine (u) NK cells that are characterized by morphology and by surface phenotyping as ''activated,'' and thus potentially damaging to the placenta, becom e localized to implantation sites during normal rodent gestation. METH OD: uNK cells migrating from explant cultures of the metrial gland wer e assessed for expression (mRNA and protein) of each chain of the IL-2 receptor (IL-2R). Implantation sites from transgenic mice lacking a f unctional IL-2 gene were examined histologically for the differentiati on of mature, granulated uNK cells. RESULTS AND CONCLUSION: Early post -implantation, mRNA from migrating uNK cells contains transcripts for all three chains of the IL-2R. Only IL-2R gamma was expressed at day 1 2 of gestation; expression of this gene was also lost by day 16. Loss of IL-2R transcription did not result in loss of protein expression; h owever, it did coincide with loss of uNK cell viability in vivo. Appar ently normal differentiation of uNK cells occurred in IL-2(-/-) mice a nd in doubly mutant IL-2(-/-).beta(2)m(-/-) mice. Thus, despite uNK ce ll expression of the full IL-2R at day 8 of gestation, IL-2 is not req uired for the maturation of uNK cells to their fully granulated form o r for normal placental development.