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Front. Immunol. | doi: 10.3389/fimmu.2018.00841

Comparison of phenotypic and functional characteristics between canine non-B, non-T NK lymphocytes and CD3+CD5dimCD21– cytotoxic large granular lymphocytes

  • 1Department of Integrated Life Science and Technology, Kongju National University, South Korea
  • 2Department of Laboratory and Companion Animal Science, Kongju National University, South Korea
  • 3Research Institute for Natural Products, Kongju National University, South Korea
  • 4Department of Hemotology-Oncology, Chonnam National University Hwasun Hospital, South Korea
  • 5Department of Radiation Oncology, Chonnam National University Hwasun Hospital, South Korea
  • 6Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, South Korea
  • 7Department of Laboratory Medicine & Genetics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, South Korea
  • 8Department of Pulmonary Immunology, The University of Texas Health Science Center at Tyler, United States
  • 9Department of Veterinary Internl Medicine, Chonnam National University, South Korea

Abstract
Natural killer (NK) cells play a pivotal role in the immune response against infections and malignant transformation, and adopted transfer of NK cells is thought to be a promising therapeutic approach for cancer patients. Previous reports describing the phenotypic features of canine NK cells have produced inconsistent results. Canine NK cells are still defined as non-B and non-T (CD3–CD21–) large granular lymphocytes. However, a few reports have demonstrated that canine NK cells share the phenotypic characteristics of T lymphocytes, and that CD3+CD5dimCD21– lymphocytes are putative canine NK cells. Based on our previous reports, we hypothesized that phenotypic modulation could occur between these two populations during activation. In this study, we investigated the phenotypic and functional differences between CD3+CD5dimCD21– (cytotoxic large granular lymphocytes, CLGLs) and CD3–CD5–CD21– NK lymphocytes before and after culture of peripheral blood mononuclear cells isolated from normal dogs. The results of this study show that CD3+CD5dimCD21– lymphocytes can be differentiated into non-B, non-T NK (CD3–CD5–CD21–TCRαβ–TCRγδ–GranzymeB+) lymphocytes through phenotypic modulation in response to cytokine stimulation. In vitro studies of purified CD3+CD5dimCD21– cells showed that CD3–CD5–CD21– cells are derived from CD3+CD5dimCD21– cells through phenotypic modulation. CD3+CD5dimCD21– cells share more NK cell functional characteristics compared with CD3–CD5–CD21– cells, including the expression of T-box transcription factors (Eomes, T-bet), the production of granzyme B and interferon-γ, and the expression of NK cell-related molecular receptors such as NKG2D and NKp30. In conclusion, the results of this study suggest that CD3+CD5dimCD21– and CD3–CD5–CD21– cells both contain a subset of putative NK cells, and the difference between the two populations may be due to the degree of maturation.

Keywords: Natural Killer cells, canine, phenotypic modulation, non-B non-T lymphocytes, CLGLs

Received: 08 Dec 2017; Accepted: 05 Apr 2018.

Edited by:

Eleanor Riley, Roslin Institute, University of Edinburgh, United Kingdom

Reviewed by:

Christy Petersen, University of Iowa, United States
Preben Boysen, Norwegian University of Life Sciences, Norway  

Copyright: © 2018 Lee, Shin, KIM, Cheol-jung, Lee, Yoon, Uong, Yu, Jung, Cho, Jung, Kim and Gukhyun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: DVM, PhD. Sang-Ki Kim, Kongju National University, Department of Integrated Life Science and Technology, Gongju, 32439, South Korea, sangki@kongju.ac.kr