The Impact of Immunodeficiency on NK Cell Maturation and Function
Purpose of Review
Natural killer cells are innate lymphoid cells (ILCs) that play critical roles in human host defense and are especially useful in combating viral pathogens and malignancy.
The NK cell deficiency (NKD) is particularly underscored in patients with a congenital immunodeficiency in which NK cell development or function is affected. The classical NK cell deficiency (cNKD) is a result of absent or a profound decrease in the number of circulating NK cells. In contrast, functional NKD (fNKD) is characterized by abnormal NK cell function but with normal number of NK cells. The combined immune deficiencies with significant impact on NK cells are not considered classical or functional NK cell deficiencies. In these disorders, the impairment of NK cells represents an important aspect of the overall immunodeficiency. In turn, this leads to improved insights on the NK cell development and function.
Here, we detail the NK cell biology based upon recent natural killer cell defects described in combined immune deficiencies.
KeywordsNatural killer cells NK cell deficiency
We acknowledge Dr. Emily Mace, for her critical review of the manuscript.
Chao Physician Scientist Junior Faculty Award, Baylor College of Medicine
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 2.•• Vargas-Hernandez A, et al. Ruxolitinib partially reverses functional natural killer cell deficiency in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations. J Allergy Clin Immunol. 2018;141(6):2142–2155 e5 This study shows that JAK inibition can partially rescue NK cell function in STAT1-GOF patients. PubMedGoogle Scholar
- 13.Kazenwadel J, Secker GA, Liu YJ, Rosenfeld JA, Wildin RS, Cuellar-Rodriguez J, et al. Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature. Blood. 2012;119(5):1283–91.PubMedPubMedCentralGoogle Scholar
- 21.Lenart M, Trzyna E, Rutkowska M, Bukowska-Strakova K, Szaflarska A, Pituch-Noworolska A, et al. The loss of the CD16 B73.1/Leu11c epitope occurring in some primary immunodeficiency diseases is not associated with the FcgammaRIIIa-48L/R/H polymorphism. Int J Mol Med. 2010;26(3):435–42.PubMedGoogle Scholar
- 35.•• Ruiz-Garcia R, et al. Mutations in PI3K110delta cause impaired natural killer cell function partially rescued by rapamycin treatment. J Allergy Clin Immunol. 2018;142(2):605–617 e7 PI3K110delta mutations impair natural killer cell function which can be partially rescued with rapamycin treatment.PubMedGoogle Scholar
- 37.•• Dobbs K, et al. Natural killer cells from patients with recombinase-activating gene and non-homologous end joining gene defects comprise a higher frequency of CD56(bright) NKG2A(+++) cells, and yet display increased degranulation and higher perforin content. Front Immunol. 2017;8:798 RAG mutations can affect NK cell maturation leading to abnormal expression of developmental markers and NK inhibitory receptors.PubMedPubMedCentralGoogle Scholar
- 39.Weinacht KG, Charbonnier LM, Alroqi F, Plant A, Qiao Q, Wu H, et al. Ruxolitinib reverses dysregulated T helper cell responses and controls autoimmunity caused by a novel signal transducer and activator of transcription 1 (STAT1) gain-of-function mutation. J Allergy Clin Immunol. 2017;139(5):1629–40 e2.PubMedPubMedCentralGoogle Scholar