CD56 identifies monocytes and not natural killer cells in rhesus macaques

Background: CD56 is a lineage-specific marker of human natural killer (NK) cells. There are conflicts in the literature regarding the role of CD56 as a marker of NK cells in non-human primates. In the present study, we examined the role of CD56 in identifying rhesus NK cells. Methods: The immunophenotype of normal macaque and human NK cells was analyzed by two- and three-color flow cytometry. Flow Cytometric cell sorting was subsequently used to deplete or purify NK cells; the resulting cell populations were then used in standard chromium release assays of NK lytic function. Results: In peripheral blood mononuclear cells of the rhesus macaque, CD56 was expressed primarily on cells with the light scatter and immunophenotypic profile of monocytes. Flow cytometric depletion of rhesus CD56⁺ monocytic cells did not diminish functional activity against K562 cells, whereas depletion of CD8⁺ or CD16⁺ lymphocytes completely abrogated functional activity. Three-color flow cytometric analysis of CD8⁺, CD16⁺ lymphocytes showed that they expressed other markers (CD2, CD7, TIA-1) associated with NK cells, but notably, not CD56. Conclusions: These studies demonstrate that CD56 is not suitable as a marker of NK cells in the rhesus macaque.