CD200S-positive granulated lymphoid cells in endometrium appear to be CD56-positive uterine NK cells

The eutopic secretory phase endometrium in endometriosis overproduces and releases a soluble immunosuppressive CD200 molecule (CD200L) and is populated by stromal cells that contain a truncated CD200 (CD200S) that promotes a proinflammatory environment. The CD200S⁺ cell population persists when pregnancy occurs and are abundant in the early pregnancy decidua of women with missed abortion. In the present study, CD200S⁺, CD56⁺, and CD68⁺ cells were enumerated in formalin-fixed paraffin-embedded tissue sections from women with endometriosis and non-endometriosis controls. CD200S⁺ cells were more numerous than CD68⁺ macrophages and were similar in number and location to CD56^bright endometrial NK cells. In some endometria, there was an additional population of CD200S^- CD56⁺ NK cells. In ectopic endometrial peritoneal deposits and in ectopic myometrial deposits (adenomyosis), CD200S⁺ cells were less frequent, consistent with the known paucity of CD56⁺ NK cells in sites of ectopic deposits. CD200S⁺ cell frequency was greater in stroma surrounding the smaller ectopic cystic deposits. Dual immunofluorescent antibody staining confirmed CD200S⁺ cells were CD56⁺ NK cells. CD200S⁺ NK cell frequency may be greater in endometriosis patients' endometrium and may affect embryo survival in early pregnancy. In our opinion, regulation of alternative splicing that results in CD200S rather than CD200L may provide new diagnostic and therapeutic options for women with endometriosis.