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CD27 Defines Phenotypically and Functionally Different Human NK Cell Subsets

Mireille T. M. Vossen^1,*,, Mourad Matmati^1,*,, Kirsten M. L. Hertoghs^1,*, Paul A. Baars^*, Mi-Ran Gent^*,, Georges Leclercq, Jörg Hamann^2,*, Taco W. Kuijpers and René A. W. van Lier^*

^* Department of Experimental Immunology and Emma Children’s Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and Department of Clinical Chemistry, Microbiology, and Immunology, University of Ghent, Ghent, Belgium

The absence of the TNF-receptor family member CD27 marks the stable acquisition of cytolytic effector functions by both CD4⁺ and CD8⁺ T cells. We found that the majority of circulating human NK cells was CD27^–. These cells were largely CD56^dim, contained high levels of perforin and granzyme B, and were able to exert strong cytotoxic activity. In contrast, circulating CD27⁺ NK cells were mostly CD56^dim/bright, had significant lower levels of perforin and granzyme B, and had a low cytolytic potential. Primary and secondary lymphoid organs were markedly enriched for CD27⁺ NK cells. When correlating the expression of CD27 to recently defined developmental stages of NK cells in tonsil, we observed that CD27 was exclusively found on mature CD94⁺, stage 4 NK cells. On these cells, regulation of CD27 expression appeared to be controlled by the common -chain cytokine IL-15, and down-regulation of CD27 was specifically induced by its ligand, CD70. Thus, the absence of CD27 expression allows the definition of cytotoxic effector cells within the known mature NK cell subsets in humans.

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¹ M.T.M.V., M.M., and K.M.L.H. contributed equally to this work.

² Address correspondence and reprint requests to Dr. J. Hamann, Department of Experimental Immunology, K0-144, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail address: j.hamann{at}amc.uva.nl

³ Abbreviations used in this paper: SLT, secondary lymphoid tissue; rh, recombinant human.