CD27‐deficient mice show normal NK‐cell differentiation but impaired function upon stimulation

Abstract

Natural killer (NK) cells are part of the first line defense against tumors, parasites and virus-infected cells. Therefore, factors that control NK-cell numbers and their function are important. CD27 is constitutively expressed on NK cells and its expression correlates with sequential phases in NK-cell development, discriminating phenotypically and functionally different subsets within the NK-cell population. Although CD27 has been described to have an important regulatory role in effector and memory T and B lymphocytes, its role in NK-cell biology remains to be addressed. In this study, we used CD27 À/À mice to investigate the role of CD27 in NK-cell development and function, both during the resting state and upon stimulation. The results show that NK-cell numbers are not impaired in CD27 À/À mice. Moreover, CD27 À/À NK cells reach full phenotypic maturity, evidenced by normal expression of CD49b, CD43 and CD11b. Expression of activating receptors is unaltered, whereas expression of several inhibitory receptors is increased. Cytotoxicity and interferon-c production by NK cells from CD27 À/À mice in the resting state are normal. However, upon in vivo anti-CD40-or poly-I:C-mediated activation, or in vitro interleukin-15 priming plus anti-NKp46 stimulation, the absence of CD27 results in decreased cytolytic activity and cytokine production by spleen and liver NK cells. In conclusion, this study demonstrates that CD27 is dispensable for the development of functional NK cells. However, upon stimulation of NK cells, CD27 displays an important role in their activation and functionality.

CD27-CD70 Costimulation Controls T Cell Immunity during Acute and Persistent Cytomegalovirus Infection

“…3C). Likely due to the low chance of separation of the CD27 gene and the Ly49 gene cluster, the Ly49H gene is missing in CD27 Ϫ/Ϫ mice backcrossed on a C57BL/6 background, which is consistent with a recent report that showed that CD27 Ϫ/Ϫ NK cells exhibit a 129/P2Ola-founded NK cell repertoire (36). To overcome this defect of Ly49H-dependent NK cell activation in CD27 Ϫ/Ϫ mice upon MCMV infection, an MCMV mutant lacking m157 (i.e., MCMV-⌬m157) was used.…”

Natural Killer Cells Are Involved in Acute Lung Immune Injury Caused by Respiratory Syncytial Virus Infection

“…NK cells can promote tissue immune injury through NKG2D, an activating receptor on NK cells, during viral infection (3,32). In addition, CD27 is a costimulated molecule and can be upregulated on NK cells after viral infection, and CD27 ϩ NK cells have a stronger function with respect to cytokine secretion and cytotoxicity (7,13,29). Thus, we measured the expression of NKG2D and CD27 on NK cells within 72 h after RSV infection.…”

Combined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27

“…Other clinically relevant consequences of CD27 dysfunction might include: i) decreased memory formation to viral (including vaccine protein) antigens; 4,26 and ii) perturbed anti-tumor immunity of T cells, 27 gdT cells, 28 and NK cells, 29,30 potentially leading to an increased risk of other malignomas in addition to EBV-lymphomas. It is likely that more individuals with dysfunctional CD27 will be identified among patient cohorts with hypogammaglobulinemia (with or without EBV-LPD) and absent CD27-expressing memory B cells, potentially leading to the recognition of CD27 deficiency as a novel, albeit probably a rare, combined immunodeficiency.…”