Skip to main content
Log in

Analysis of the CD161-expressing cell quantities and CD161 expression levels in peripheral blood natural killer and T cells of systemic lupus erythematosus patients

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Expressed on the cell surface of most of NK cells and some T cells, CD161 has been shown to deliver inhibitory signal in human NK cells. To determine whether the CD161-expressing cell quantities and the cell surface expression levels of CD161 in NK and T cells were altered in systemic lupus erythematosus (SLE) patients, we analyzed the CD3, CD56 and CD161 expression patterns of peripheral blood lymphocytes by flow cytometric analysis to identify different NK and T cell subpopulations. The cell surface expression levels of CD161 were estimated by the mean florescence intensities (MFIs) of CD161. It was found that SLE patients had lower frequencies of CD161+CD56+CD3− and CD161+CD56+CD3+ cells among the lymphocyte population than normal controls, whereas the frequencies of CD161−CD56+CD3− and CD161+CD56−CD3+ cells were not statistically different between two groups. In addition, SLE patients also had decreased absolute counts of all CD161-expressing NK cells and T cells and had reduced frequencies of CD161+ cells in CD56+CD3−, CD56+CD3+ and CD56−CD3+ cell populations. Moreover, SLE patients had reduced MFIs of CD161 in CD161+CD56+CD3+ and CD161+CD56−CD3+, but not CD161+CD56+CD3−, cell populations. Our results indicated that CD161-expressing cell frequency and the CD161 expression levels were reduced in some NK and T cell subpopulations of SLE patients, suggesting possible important role of CD161 and CD161-expressing immune cells in the SLE pathogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Sibbitt WL Jr, Mathews PM, Bankhurst AD. Natural killer cell in systemic lupus erythematosus. Defects in effector lytic activity and response to interferon and interferon inducers. J Clin Invest. 1983;71:1230–9.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Yabuhara A, Yang FC, Nakazawa T, et al. A killing defect of natural killer cells as an underlying immunologic abnormality in childhood systemic lupus erythematosus. J Rheumatol. 1996;23:171–7.

    CAS  PubMed  Google Scholar 

  3. Stohl W, Elliott JE, Hamilton AS, Deapen DM, Mack TM, Horwitz DA. Impaired recovery and cytolytic function of CD56+ T and non-T cells in systemic lupus erythematosus following in vitro polyclonal T cell stimulation. Studies in unselected patients and monozygotic disease-discordant twins. Arthritis Rheum. 1996;39:1840–51.

    Article  CAS  PubMed  Google Scholar 

  4. Erkeller-Yuksel FM, Lydyard PM, Isenberg DA. Lack of NK cells in lupus patients with renal involvement. Lupus. 1997;6:708–12.

    Article  CAS  PubMed  Google Scholar 

  5. Riccieri V, Spadaro A, Parisi G, et al. Down-regulation of natural killer cells and of γ/δ T cells in systemic lupus erythematosus. Does it correlate to autoimmunity and to laboratory indices of disease activity? Lupus. 2000;9:333–7.

    Article  CAS  PubMed  Google Scholar 

  6. Park Y-W, Kee S-J, Cho Y-N, et al. Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythematosus. Arthritis Rheum. 2009;60:1753–63.

    Article  CAS  PubMed  Google Scholar 

  7. Cho Y-N, Kee S-J, Lee S-J, et al. Numerical and functional deficiencies of natural killer T cells in systemic lupus erythematosus: their deficiency related to disease activity. Rheumatology. 2011;50:1054–63.

    Article  CAS  PubMed  Google Scholar 

  8. Hervier B, Beziat V, Haroche J, et al. Phenotype and function of natural killer cells in systemic lupus erythematosus: excess interferon-γ production in patients with active disease. Arthritis Rheum. 2011;63:1698–706.

    Article  CAS  PubMed  Google Scholar 

  9. Puxeddu I, Bongiorni F, Chimenti D, et al. Cell surface expression of activating receptors and co-receptors on peripheral blood NK cells in systemic autoimmune diseases. Scand J Rheumatol. 2012;41:298–304.

    Article  CAS  PubMed  Google Scholar 

  10. Henriques A, Teixeira L, Inês L, et al. NK cells dysfunction in systemic lupus erythematosus: relation to disease activity. Clin Rheumatol. 2013;32:805–13.

    Article  PubMed  Google Scholar 

  11. Shi FD, Van Kaer L. Reciprocal regulation between natural killer cells and autoreactive T cells. Nat Rev Immunol. 2006;6:751–60.

    Article  CAS  PubMed  Google Scholar 

  12. Wu W, Shi S, Ljunggren H-G, et al. NK cells inhibit T-bet-deficient, autoreactive Th17 cells. Scand J Immunol. 2012;76:559–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fogel LA, Yokoyama WM, French AR. Natural killer cells in human autoimmune disorders. Arthritis Res Ther. 2013;15:216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mesci A, Ljutic B, Makrigiannis AP, Carlyle JR. NKR-P1 biology: from prototype to missing self. Immunol Res. 2006;35:13–26.

    Article  CAS  PubMed  Google Scholar 

  15. Lanier LL, Chang C, Phillips JH. Human NKR-P1A. A disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. J Immunol. 1994;153:2417–28.

    CAS  PubMed  Google Scholar 

  16. Takahashi T, Dejbakhsh-Jones S, Strober S. Expression of CD161 (NKR-P1A) defines subsets of human CD4 and CD8 T cells with different functional activities. J Immunol. 2006;176:211–6.

    Article  CAS  PubMed  Google Scholar 

  17. Billerbeck E, Kang Y-H, Walker L, et al. Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. Proc Natl Acad Sci USA. 2010;107:3006–11.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cosmi L, De Palma R, Santarlasci V, et al. Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor. J Exp Med. 2008;205:1903–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Maggi L, Santarlasci V, Capone M, et al. CD161 is a marker of all human IL-17-producing T-cell subsets and is induced by RORC. Eur J Immunol. 2010;40:2174–81.

    Article  CAS  PubMed  Google Scholar 

  20. Pesenacker AM, Bending D, Ursu S, Wu Q, Nistala K, Wedderburn LR. CD161 defines the subset of FoxP3+ T cells capable of producing proinflammatory cytokines. Blood. 2013;121:2647–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Aldemir H, Prod’homme V, Dumaurier M-J, et al. Cutting edge: lectin-like transcript 1 is a ligand for the CD161 receptor. J Immunol. 2005;175:7791–5.

    Article  CAS  PubMed  Google Scholar 

  22. Rosen DB, Bettadapura J, Alsharifi M, Mathew PA, Warren HS, Lanier LL. Cutting edge: lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor. J Immunol. 2005;175:7796–9.

    Article  CAS  PubMed  Google Scholar 

  23. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25:1271–7.

    Article  CAS  PubMed  Google Scholar 

  24. Bombardier C, Gladman D, Urowitz M, Caron D, Chang C. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992;35:630–40.

    Article  CAS  PubMed  Google Scholar 

  25. Mitsuo A, Morimoto S, Nakiri Y, et al. Decreased CD161+CD8+ T cells in the peripheral blood of patients suffering from rheumatic diseases. Rheumatology. 2006;45:1477–84.

    Article  CAS  PubMed  Google Scholar 

  26. Chalan P, Kroesen B-J, van der Geest KSM, et al. Circulating CD4+CD161+ T lymphocytes are increased in seropositive arthralgia patients but decreased in patients with newly diagnosed rheumatoid arthritis. PLoS One. 2013;8:e79370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li W-X, Pan H-F, Hu J-L, et al. Assay of T- and NK-cell subsets and the expression of NKG2A and NKG2D in patients with new-onset systemic lupus erythematosus. Clin Rheumatol. 2010;29:315–23.

    Article  PubMed  Google Scholar 

  28. Bai Y, Zhang Y, Yang Q, et al. The aberrant expression of stimulatory and inhibitory killer immunoglobulin-like receptors in NK- and NKT-cells contributes to lupus. Clin Lab. 2014;60:717–27.

    CAS  PubMed  Google Scholar 

  29. Schepis D, Gunnarsson I, Eloranta M-L, et al. Increased proportion of CD56bright natural killer cells in active and inactive systemic lupus erythematosus. Immunology. 2009;126:140–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bedoya SK, Lam B, Lau K, Larkin J III. Th17 cells in immunity and autoimmunity. Clin Dev Immunol. 2013;2013:986789.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

I thank Yanfeng Lu for review of the manuscript. This study was supported by a grant from the joined research found of Cathay General Hospital and National Taiwan University and by a grant from the National Science Council of Taiwan (Grant#101-2314-B-281-006).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shih-Chang Lin.

Ethics declarations

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, YL., Lin, SC. Analysis of the CD161-expressing cell quantities and CD161 expression levels in peripheral blood natural killer and T cells of systemic lupus erythematosus patients. Clin Exp Med 17, 101–109 (2017). https://doi.org/10.1007/s10238-015-0402-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-015-0402-1

Keywords

Navigation