A distinct distribution of natural killer cell subgroups in human tissues and blood

Natural killer (NK) cells have been subdivided according to their CD16/CD56 expression into at least 2 subgroups. We examined the distribution of these NK subgroups in humans. In the blood of normal individuals, CD16++/CD56+/CD3- NK cells predominate, constituting more than 90% of all NK cells. In contrast, decidua is infiltrated almost exclusively by CD16(+/-)/CD56+/CD3- NK cells (>90%), a fact so far seen in context with decidua being an immunoprivileged tissue. However, this NK subgroup can also be detected in the blood, where it comprises about 10% of NK cells. We have found that normal (colon) as well as neoplastic (ovarian and urothelial carcinoma) tissues are also predominantly infiltrated by this CD16+/- NK subgroup. Lymphatic fluid draining solid tissues contains CD16+/- NK cells exclusively, with absolute numbers of NK cells being very low. No predominating NK subgroup was seen in ascites. CD16+/- NK cells, when tested against the target cell lines K562 and JAR, revealed a cytotoxic spectrum different from CD16++ NK cells and from T cells. A change in the CD16/CD56/CD3 phenotype was not seen in either subgroup in long-term cultures containing IL-2 (1,000 U/ml). Our data indicate that the decidua is not the only solid tissue infiltrated by CD16+/- NK cells. Other normal and malignant tissues were also infiltrated predominantly by this NK cell subgroup. We suggest that CD16+/- NK cells represent a functionally distinct NK subgroup involved in the surveillance of solid tissues.