Expansion of CD4 phenotype among CD160 receptor-expressing lymphocytes in murine pregnancy
Matyas Meggyes
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Janos Szentagothai Research Centre, Pecs, Hungary
Search for more papers by this authorLaszlo Szereday
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Janos Szentagothai Research Centre, Pecs, Hungary
Search for more papers by this authorPal Jakso
Department of Pathology, Medical School, University of Pecs, Pecs, Hungary
Search for more papers by this authorBarbara Bogar
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Search for more papers by this authorAgnes Bogdan
Janos Szentagothai Research Centre, Pecs, Hungary
Department of Medical Biology, Medical School, University of Pecs, Pecs, Hungary
Search for more papers by this authorJasper Nörenberg
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Search for more papers by this authorEva Miko
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Janos Szentagothai Research Centre, Pecs, Hungary
Search for more papers by this authorCorresponding Author
Aliz Barakonyi
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Janos Szentagothai Research Centre, Pecs, Hungary
Correspondence
Aliz Barakonyi, Department of Medical Microbiology and Immunology, University of Pecs, Medical School, Pecs, Hungary.
Email: [email protected]
Search for more papers by this authorMatyas Meggyes
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Janos Szentagothai Research Centre, Pecs, Hungary
Search for more papers by this authorLaszlo Szereday
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Janos Szentagothai Research Centre, Pecs, Hungary
Search for more papers by this authorPal Jakso
Department of Pathology, Medical School, University of Pecs, Pecs, Hungary
Search for more papers by this authorBarbara Bogar
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Search for more papers by this authorAgnes Bogdan
Janos Szentagothai Research Centre, Pecs, Hungary
Department of Medical Biology, Medical School, University of Pecs, Pecs, Hungary
Search for more papers by this authorJasper Nörenberg
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Search for more papers by this authorEva Miko
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Janos Szentagothai Research Centre, Pecs, Hungary
Search for more papers by this authorCorresponding Author
Aliz Barakonyi
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary
Janos Szentagothai Research Centre, Pecs, Hungary
Correspondence
Aliz Barakonyi, Department of Medical Microbiology and Immunology, University of Pecs, Medical School, Pecs, Hungary.
Email: [email protected]
Search for more papers by this authorAbstract
Problem
CD160, a cell surface co-receptor, is capable of up- or downregulating cell proliferation, cytotoxicity or cytokine production on lymphocytes. Our aim was to investigate CD160+ lymphocytes in the periphery and at the maternal-foetal interface during murine pregnancy.
Method of study
CD4+, CD8+ and gamma/delta T-cell phenotype, TIM3 co-expression and cytotoxic activity of CD160+ lymphocytes of pregnant BALB/c mice were analysed by flow cytometry.
Results
The percentage of CD160+ lymphocytes in the decidua was unchanged compared to non-pregnant endometrium; however, the ratio of CD4+ cells within the CD160 population was significantly increased. The co-expression of TIM3 co-inhibitory molecule and cytotoxicity of CD160+ cells were increased in the decidua.
Conclusion
The expansion of CD4-expressing CD160+ decidual lymphocytes is a new observation suggesting a potential regulatory role of T-cell function during mouse pregnancy. The altered immunological character of CD160+ lymphocytes could play a role in the maintenance of murine pregnancy.
REFERENCES
- 1Maïza H, Leca G, Mansur IG, Schiavon V, Boumsell L, Bensussan A. A novel 80-kD cell surface structure identifies human circulating lymphocytes with natural killer activity. J Exp Med. 1993; 178: 1121-1126.
- 2Bensussan A, Rabian C, Schiavon V, Bengoufa D, Leca G, Boumsell L. Significant enlargement of a specific subset of CD3+CD8+ peripheral blood leukocytes mediating cytotoxic T-lymphocyte activity during human immunodeficiency virus infection. Proc Natl Acad Sci USA. 1993; 90: 9427-9430.
- 3Anumanthan A, Bensussan A, Boumsell L, et al. Cloning of BY55, a novel Ig superfamily member expressed on NK cells, CTL, and intestinal intraepithelial lymphocytes. J Immunol. 1998; 161: 2780-2790.
- 4Cai G, Anumanthan A, Brown JA, Greenfield EA, Zhu B, Freeman GJ. CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator. Nat Immunol. 2008; 9: 176-185.
- 5Agrawal S, Marquet J, Freeman GJ, et al. Cutting edge: MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T cells. J Immunol. 1999; 162: 1223-1226.
- 6Le Bouteiller P, Barakonyi A, Giustiniani J, et al. Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity. Proc Natl Acad Sci USA. 2002; 99: 16963-16968.
- 7Giustiniani J, Bensussan A, Marie-Cardine A. Identification and characterization of a transmembrane isoform of CD160 (CD160-TM), a unique activating receptor selectively expressed upon human NK cell activation. J Immunol. 2009; 182: 63-71.
- 8Giustiniani J, Marie-Cardine A, Bensussan A. A soluble form of the MHC class I-specific CD160 receptor is released from human activated NK lymphocytes and inhibits cell-mediated cytotoxicity. J Immunol. 2007; 178: 1293-1300.
- 9Barakonyi A, Rabot M, Marie-Cardine A, et al. Cutting edge: engagement of CD160 by its HLA-C physiological ligand triggers a unique cytokine profile secretion in the cytotoxic peripheral blood NK cell subset. J Immunol. 2004; 173: 5349-5354.
- 10Nikolova MH, Muhtarova MN, Taskov HB, et al. The CD160+ CD8high cytotoxic T cell subset correlates with response to HAART in HIV-1+ patients. Cell Immunol. 2005; 237: 96-105.
- 11Peretz Y, He Z, Shi Y, et al. CD160 and PD-1 co-expression on HIV-specific CD8 T cells defines a subset with advanced dysfunction. PLoS Pathog. 2012; 8: e1002840.
- 12Chibueze CE, Yoshimitsu M, Arima N. CD160 expression defines a uniquely exhausted subset of T lymphocytes in HTLV-1 infection. Biochem Biophys Res Commun. 2014; 453: 379-384.
- 13Rozot V, Vigano S, Mazza-Stalder J, et al. Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease. Eur J Immunol. 2013; 43: 1568-1577.
- 14Merino J, Ramírez N, Moreno C, Toledo E, Fernández M, Sánchez-Ibarrola A. BY55/CD160 cannot be considered a cytotoxic marker in cytomegalovirus-specific human CD8(+) T cells. Clin Exp Immunol. 2007; 149: 87-96.
- 15Cheung TC, Steinberg MW, Oborne LM, et al. Unconventional ligand activation of herpesvirus entry mediator signals cell survival. Proc Natl Acad Sci USA. 2009; 106: 6244-6249.
- 16Gill RM, Coleman NM, Hunt JS. Differential cellular expression of LIGHT and its receptors in early gestation human placentas. J Reprod Immunol. 2007; 74: 1-6.
- 17Gill RM, Ni J, Hunt JS. Differential expression of LIGHT and its receptors in human placental villi and amniochorion membranes. Am J Pathol. 2002; 161: 2011-2017.
- 18Chang YH, Hsieh SL, Chao Y, Chou YC, Lin WW. Proinflammatory effects of LIGHT through HVEM and LTbetaR interactions in cultured human umbilical vein endothelial cells. J Biomed Sci. 2005; 12: 363-375.
- 19Takahashi N, Sato N, Takahashi S, Tojo A. Gene-expression profiles of peripheral blood mononuclear cell subpopulations in acute graft-vs-host disease following cord blood transplantation. Exp Hematol. 2008; 36: 1760-1770.
- 20El Costa H, Tabiasco J, Berrebi A, et al. Effector functions of human decidual NK cells in healthy early pregnancy are dependent on the specific engagement of natural cytotoxicity receptors. J Reprod Immunol. 2009; 82: 142-147.
- 21Wallace Alison E, Whitley Guy S, Thilaganathan Baskaran, Cartwright Judith E. Decidual natural killer cell receptor expression is altered in pregnancies with impaired vascular remodeling and a higher risk of pre-eclampsia. J Leukoc Biol. 2015; 97: 79-86.
- 22Aktas E, Kucuksezer UC, Bilgic S, Erten G, Deniz G. Relationship between CD107a expression and cytotoxic activity. Cell Immunol. 2009; 254: 149-154.
- 23Maeda M, Carpenito C, Russell RC, et al. Murine CD160, Ig-like receptor on NK cells and NKT cells, recognizes classical and nonclassical MHC class I and regulates NK cell activation. J Immunol. 2005; 175: 4426-4432.
- 24Nikolova M, Marie-Cardine A, Boumsell L, Bensussan A. BY55/CD160 acts as a co-receptor in TCR signal transduction of a human circulating cytotoxic effector T lymphocyte subset lacking CD28 expression. Int Immunol. 2002; 14: 445-451.
- 25D'Addio F, Ueno T, Clarkson M, et al. CD160Ig fusion protein targets a novel costimulatory pathway and prolongs allograft survival. PLoS ONE. 2013; 8: e60391.
- 26El-Far M, Pellerin C, Pilote L, et al. CD160 isoforms and regulation of CD4 and CD8 T-cell responses. J Transl Med. 2014; 12: 217-232.
- 27Abecassis S, Giustiniani J, Meyer N, et al. Identification of a novel CD160+ CD4+ T-lymphocyte subset in the skin: a possible role for CD160 in skin inflammation. J Invest Dermatol. 2007; 127: 1161-1166.
- 28Tsujimura K, Obata Y, Matsudaira Y, et al. Characterization of murine CD160+ CD8+ T lymphocytes. Immunol Lett. 2006; 106: 48-56.
- 29Yamamoto T, Price DA, Casazza JP, et al. Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood. 2011; 117: 4805-4815.
- 30Bengsch B, Seigel B, Ruhl M, et al. Coexpression of PD-1, 2B4, CD160 and KLRG1 on exhausted HCV-specific CD8+ T cells is linked to antigen recognition and T cell differentiation. PLoS Pathog. 2010; 6: e1000947.
- 31Tao R, Wang L, Murphy KM, Fraser CC, Hancock WW. Regulatory T cell expression of herpesvirus entry mediator suppresses the function of B and T lymphocyte attenuator-positive effector T cells. J. Immunol. 2008; 180: 6649-6655.
- 32Parkes MD, Halloran PF, Hidalgo LG. Mechanistic sharing between NK cells in ABMR and effector T cells in TCMR. Am J Transplant 2017; [Epub ahead of print], http://org.doi:10.1111/ajt.14410.
