NDLI: Human Natural Killer Cell Maturation Defect Supports In Vivo CD56bright to CD56dim Lineage Development

Content Provider	PubMed Central
Author	Domaica, Carolina Inés Fuertes, Mercedes Beatriz Uriarte, Ignacio Victoria, Girart María Jessica, Sardañons Comas, Dorina Ileana Giovanni, Daniela Di Gaillard, María Isabel Bezrodnik, Liliana Zwirner, Norberto Walter
Editor	Ahlenstiel, Golo
Copyright Year	2012
Abstract	Two populations of human natural killer (NK) cells can be identified in peripheral blood. The majority are CD3−CD56dim cells while the minority exhibits a CD3−CD56bright phenotype. In vitro evidence indicates that CD56bright cells are precursors of CD56dim cells, but in vivo evidence is lacking. Here, we studied NK cells from a patient that suffered from a melanoma and opportunistic fungal infection during childhood. The patient exhibited a stable phenotype characterized by a reduction in the frequency of peripheral blood CD3−CD56dim NK cells, accompanied by an overt increase in the frequency and absolute number of CD3−CD56bright cells. These NK cells exhibited similar expression of perforin, CD57 and CD158, the major activating receptors CD16, NKp46, NKG2D, DNAM-1, and 2B4, as well as the inhibitory receptor CD94/NKG2A, on both CD56bright and CD56dim NK cells as healthy controls. Also, both NK cell subpopulations produced IFN-γ upon stimulation with cytokines, and CD3−CD56dim NK cells degranulated in response to cytokines or K562 cells. However, upon stimulation with cytokines, a substantial fraction of CD56dim cells failed to up-regulate CD57 and CD158, showed a reduction in the percentage of CD16+ cells, and CD56bright cells did not down-regulate CD62L, suggesting that CD56dim cells could not acquire a terminally differentiated phenotype and that CD56bright cells exhibit a maturation defect that might result in a potential altered migration pattern. These observations, support the notion that NK cells of this patient display a maturation/activation defect that precludes the generation of mature NK cells at a normal rate accompanied by CD56dim NK cells that cannot completely acquire a terminally differentiated phenotype. Thus, our results provide evidence that support the concept that in vivo CD56bright NK cells differentiate into CD56dim NK cells, and contribute to further understand human NK cell ontogeny.
Related Links	http://dx.doi.org/10.1371/journal.pone.0051677
Starting Page	51677
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	12
Volume Number	7
Language	English
Publisher	Public Library of Science
Publisher Date	2012-12-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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