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Published on: April 16, 2015
CD27-deficient mice show normal NK-cell differentiation but impaired function upon stimulation
Veerle De Colvenaer1, Sylvie Taveirne, Maarten Delforche
1Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
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(-/-) 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(-/-) mice. Moreover, CD27(-/-) 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-γ production by NK cells from CD27(-/-) 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.
Insights
CD27 is not essential for natural killer (NK) cell development or resting function. However, this study shows CD27 is crucial for optimal NK cell activation and effector functions following stimulation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Natural killer (NK) cells are vital for innate immunity against pathogens and tumors.
- CD27 expression on NK cells changes during development and influences subset function.
- The specific role of CD27 in NK cell biology requires further investigation.
Purpose of the Study:
- To investigate the role of CD27 in NK cell development and function using CD27-deficient mice.
- To assess NK cell phenotype, cytotoxicity, and cytokine production in both resting and stimulated states.
Main Methods:
- Utilized CD27(-/-) mice to study NK cell development and function.
- Analyzed NK cell populations for surface marker expression (CD49b, CD43, CD11b).
- Assessed NK cell cytotoxicity and interferon-gamma production under resting and stimulated conditions (in vivo and in vitro).
Main Results:
- NK cell numbers and maturation were normal in CD27(-/-) mice.
- Expression of activating receptors remained unchanged, while inhibitory receptors increased.
- Resting NK cell cytotoxicity and interferon-gamma production were unaffected.
- Stimulated NK cells from CD27(-/-) mice showed reduced cytotoxicity and cytokine production.
Conclusions:
- CD27 is dispensable for the development of functional NK cells.
- CD27 plays a significant role in enhancing NK cell activation and effector functions upon stimulation.
