Head J R, Kresge C K, Young J D, Hiserodt J C
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235-9051.
Biol Reprod. 1994 Sep;51(3):509-23. doi: 10.1095/biolreprod51.3.509.
An intriguing component of the maternal response to pregnancy is the differentiation of large numbers of large granular lymphocytes, termed granulated metrial gland (GMG) cells, in the decidua and then in the metrial gland, a structure in the mesometrial triangle unique to rodent pregnancy. We have used the monoclonal antibody 3.2.3 to NKR-P1, a surface molecule involved in triggering natural killer (NK) cells for lysis, to determine the numbers and distribution of NK cells in the nonpregnant rat uterus and during the dramatic changes at implant sites during pregnancy. NKR-P1+ cells were abundant in the nonpregnant uterus, especially in the endometrium. These cells also expressed CD8, CD2, and AsialoGM1. In the subepithelial stroma, the numbers were greatest during proestrus and estrus; in ovariectomized animals, they were severely decreased, but returned to normal with estrogen supplementation. At the time of blastocyst attachment (Day 6), NKR-P1+ cells were few around the implant and in the decidualizing stroma. However, on Day 8, substantial numbers were present in the mesometrial decidua only, and many of these cells expressed the cytolytic protein perforin. By Day 10, NKR-P1+ cells were common within the inner muscle at the base of the mesometrial triangle and in the developing metrial gland, often containing perforin. Larger numbers of perforin+ cells were present in the central decidua towards the ectoplacental cone, and many were weakly NKR-P1+ only. On Day 12, NKR-P1+ cells were almost completely restricted to the metrial gland, with few in decidua, and many were weakly positive. Substantially more perforin-containing cells were seen, indicating that many had lost detectable NKR-P1. This distribution pattern from Days 6-12 is similar to that described for GMG cells and demonstrates that in the rat they belong to the NK cell lineage. These cells were also CD8+ and AsialoGM1+ but negative for CD2 and class II histocompatibility antigens, which is very different from interleukin-2-activated NK cells which they resemble morphologically. The loss during differentiation of NKR-P1 and CD2, which are involved in target adhesion and triggering of NK cells, is consistent with the poor cytolytic capacity reported for these cells.
母体对妊娠反应的一个有趣组成部分是，大量大颗粒淋巴细胞（称为颗粒状子宫蜕膜细胞，即GMG细胞）在蜕膜中分化，然后在子宫蜕膜腺中分化，子宫蜕膜腺是啮齿动物妊娠特有的子宫系膜三角区中的一种结构。我们使用了针对NKR-P1的单克隆抗体3.2.3，NKR-P1是一种参与触发自然杀伤（NK）细胞进行裂解的表面分子，来确定未孕大鼠子宫中NK细胞的数量和分布，以及妊娠期间着床部位发生显著变化时NK细胞的数量和分布。NKR-P1+细胞在未孕子宫中大量存在，尤其是在内膜中。这些细胞还表达CD8、CD2和去唾液酸GM1。在子宫上皮下基质中，细胞数量在动情前期和动情期最多；在去卵巢动物中，细胞数量严重减少，但补充雌激素后恢复正常。在胚泡着床时（第6天），着床部位周围和蜕膜化基质中的NKR-P1+细胞很少。然而，在第8天，大量NKR-P1+细胞仅存在于子宫系膜侧蜕膜中，其中许多细胞表达溶细胞蛋白穿孔素。到第10天，NKR-P1+细胞在子宫系膜三角底部的内层肌层和发育中的子宫蜕膜腺中很常见，通常含有穿孔素。在靠近外胎盘锥的中央蜕膜中有更多的穿孔素+细胞，许多细胞仅为弱阳性NKR-P1+。在第12天，NKR-P1+细胞几乎完全局限于子宫蜕膜腺，蜕膜中很少，许多细胞为弱阳性。可见大量含穿孔素的细胞，表明许多细胞已失去可检测到的NKR-P1。第6至12天的这种分布模式与GMG细胞的分布模式相似，表明在大鼠中它们属于NK细胞谱系。这些细胞也是CD8+和去唾液酸GM1+，但CD2和II类组织相容性抗原为阴性，这与它们在形态上相似的白细胞介素-2激活的NK细胞非常不同。参与NK细胞与靶细胞黏附及触发的NKR-P1和CD2在分化过程中的丢失，与这些细胞报道的弱溶细胞能力一致。
