The differential expression of CD4- CD8- double negative T lymphocytes in neuromyelitis optica spectrum disorders and multiple sclerosis

doi:10.3969/j.issn.1672-6731.2020.09.006

Abstract

Abstract:

Objective To compare the levels of CD4^-CD8^- double negative T lymphocytes(DNT) in the peripheral blood of patients with neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS) in the acute phase. Methods From January 2017 to December 2019, a total of 53 patients with NMOSDs, 20 patients with MS and 27 normal controls were included. Peripheral blood DNT cells of the patients in 3 groups were measured by flow cytometry. Results The differences of DNT cells in the peripheral blood in 3 groups were statistically significant (F=4.362, P=0.015). Among them, the number of DNT cells in the NMOSDs group was higher than that in the control group (t=2.415, P=0.023) and the MS group (t=2.415, P=0.018), while the number of DNT cells in the MS group and the control group was not statistically different (t=0.149, P=0.881). Conclusions The number of DNT cells in the peripheral blood of patients with NMOSDs in the acute phase is higher than that in patients with MS and normal controls. It is speculated that DNT cells may be involved in the pathogenesis of NMOSDs.

Key words: Neuromyelitis optica, Multiple sclerosis, T-lymphocyte subsets, Flow cytometry

摘要：

目的对比分析视神经脊髓炎谱系疾病（NMOSDs）与多发性硬化患者急性期外周血CD4^-CD8^-双阴性T细胞（DNT）表达差异。方法纳入2017年1月至2019年12月诊断明确的NMOSDs（53例）和多发性硬化（20例）患者，以及性别、年龄相匹配的正常对照者（27例），流式细胞术测定外周血DNT细胞数目。结果 3组受试者外周血DNT细胞数目差异具有统计学意义（F=4.362，P=0.015），其中NMOSDs组DNT细胞数目分别高于正常对照组（t=2.415，P=0.023）和多发性硬化组（t=2.415，P=0.018），而多发性硬化组与正常对照组DNT细胞数目差异无统计学意义（t=0.149，P=0.881）。。结论 NMOSDs急性期患者外周血DNT细胞数目高于多发性硬化患者和正常对照者，推测DNT细胞可能参与NMOSDs的发病机制。

关键词: 视神经脊髓炎, 多发性硬化, T淋巴细胞亚群, 流式细胞术

SHA Jing, YANG Li-juan, Mayinuer Maimaiti, LI Hong-yan. The differential expression of CD4^- CD8^- double negative T lymphocytes in neuromyelitis optica spectrum disorders and multiple sclerosis[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(9): 788-793.

沙晶, 杨丽娟, 玛依努尔·买买提, 李红燕. CD4^-CD8^-双阴性T淋巴细胞在视神经脊髓炎谱系疾病与多发性硬化中的表达差异[J]. 中国现代神经疾病杂志, 2020, 20(9): 788-793.

/ / Recommend / Download Citations

URL: http://journal11.magtechjournal.com/cjcnn/EN/10.3969/j.issn.1672-6731.2020.09.006

http://journal11.magtechjournal.com/cjcnn/EN/Y2020/V20/I9/788

References

[1] Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitisoptica[J]. Lancet Neurol, 2007, 6:805-815.
[2] Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis[J]. Nat Rev Immunol, 2015, 15:545-558.
[3] Wingerchuk DM, Hogancamp WF, O'Brien PC, Weinshenker BG. The clinical course of neuromyelitisoptica (Devic's syndrome)[J]. Neurology, 1999, 53:1107-1114.
[4] Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG. A serum autoantibody marker of neuromyelitisoptica:distinction from multiple sclerosis[J]. Lancet, 2004, 364:2106-2112.
[5] Lai ZW, Borsuk R, Shadakshari A, Yu J, Dawood M, Garcia R, Francis L, Tily H, Bartos A, Faraone SV, Phillips P, Perl A. Mechanistic target of rapamycin activation triggers IL-4 production and necrotic death of double-negative T cells in patients with systemic lupus erythematosus[J]. J Immunol, 2013, 191:2236-2246.
[6] Collin R, Lombard-Vadnais F, Hillhouse EE, Lebel M, Chabot-Roy G, Melichar HJ, Lesage S. MHC-independent thymic selection of CD4 and CD8 coreceptor negative αβ T cells[J]. J Immunol, 2020, 205:133-142.
[7] Chen W, Ford MS, Young KJ, Zhang L. The role and mechanisms of double negative regulatory T cells in the suppression of immune responses[J]. Cell Mol Immunol, 2004, 1:328-335.
[8] Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitisoptica spectrum disorders[J]. Neurology, 2015, 85:177-189.
[9] Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintoré M, Traboulsee AL, Trojano M, Uitdehaag BM, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis:2017 revisions of the McDonald criteria[J]. Lancet Neurol, 2018, 17:162-173.
[10] Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Wegner B, Hellwig K, Pache F, Ruprecht K, Havla J, Krumbholz M, Kümpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker R, Schwab M, Marziniak M, Bergh FT, van Oy UH, Neuhaus O, Winkelmann A, Marouf W, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C; Neuromyelitis Optica Study Group. Neuromyelitisoptica:evaluation of 871 attacks and 1, 153 treatment courses[J]. Ann Neurol, 2016, 79:206-216.
[11] Kurtzke JF. Rating neurologic impairment in multiple sclerosis:an expanded disability status scale (EDSS)[J]. Neurology, 1983, 33:1444-1452.
[12] Lindsey JW, Meulmester KM, Brod SA, Nelson F, Wolinsky JS. Variable results after rituximab in neuromyelitisoptica[J]. J Neurol Sci, 2012, 317:103-105.
[13] Liapis K, Tsagarakis NJ, Panitsas F, Taparkou A, Liapis I, Roubakis C, Tsokanas D, Vasileiou P, Grigoriou E, Kakiopoulos G, Psarra K, Farmaki E, Paterakis G. Causes of double-negative T-cell lymphocytosis in children and adults[J]. J Clin Pathol, 2020, 73:431-438.
[14] Brandt D, Hedrich CM. TCRαβ(+)CD3(+)CD4(-)CD8(-) (double negative) T cells in autoimmunity[J]. Autoimmun Rev, 2018, 17:422-430.
[15] Hedrich CM, Rauen T, Crispin JC, Koga T, Ioannidis C, Zajdel M, Kyttaris VC, Tsokos GC. cAMP-responsive element modulator α (CREM α) trans-represses the transmembrane glycoprotein CD8 and contributes to the generation of CD3+ CD4-CD8-T cells in health and disease[J]. J Biol Chem, 2013, 288:31880-31887.
[16] Priatel JJ, Utting O, Teh HS. TCR/self-antigen interactions drive double-negative T cell peripheral expansion and differentiation into suppressor cells[J]. J Immunol, 2001, 167:6188-6194.
[17] Bleesing JJ, Brown MR, Dale JK, Straus SE, Lenardo MJ, Puck JM, Atkinson TP, Fleisher TA. TCR-alpha/beta(+) CD4(-)CD8(-) T cells in humans with the autoimmune lymphoproliferative syndrome express a novel CD45 isoform that is analogous to murine B220 and represents a marker of altered O-glycan biosynthesis[J]. Clin Immunol, 2001, 100:314-324.
[18] Haug T, Aigner M, Peuser MM, Strobl CD, Hildner K, Mougiakakos D, Bruns H, Mackensen A, Völkl S. Human double-negative regulatory T-cells induce a metabolic and functional switch in effector T-cells by suppressing mTOR activity[J]. Front Immunol, 2019, 10:883.
[19] D'Acquisto F, Crompton T. CD3+ CD4-CD8-(double negative) T cells:saviours or villains of the immune response[J]. Biochem Pharmacol, 2011, 82:333-340.
[20] Reinhardt C, Melms A. Normalization of elevated CD4-/CD8-(double-negative) T cells after thymectomy parallels clinical remission in myasthenia gravis associated with thymic hyperplasia but not thymoma[J]. Ann Neurol, 2000, 48:603-608.
[21] Crispín JC, Tsokos GC. IL-17 in systemic lupus erythematosus[J]. J Biomed Biotechnol, 2010:ID943254.
[22] Li H, Adamopoulos IE, Moulton VR, Stillman IE, Herbert Z, Moon JJ, Sharabi A, Krishfield S, Tsokos MG, Tsokos GC. Systemic lupus erythematosus favors the generation of IL-17 producing double negative T cells[J]. Nat Commun, 2020, 11:2859.
[23] Matsumoto Y, Abe S, Tsuchida M, Hirahara H, Abo T, Shin T, Tanuma N, Kojima T, Ishihara Y. Characterization of CD4-CD8-T cell receptor alpha beta + T cells appearing in the subarachnoid space of rats with autoimmune encephalomyelitis[J]. Eur J Immunol, 1996, 26:1328-1334.
[24] Meng H, Zhao H, Cao X, Hao J, Zhang H, Liu Y, Zhu MS, Fan L, Weng L, Qian L, Wang X, Xu Y. Double-negative T cells remarkably promote neuroinflammation after ischemic stroke[J]. Proc Natl Acad Sci USA, 2019, 116:5558-5563.
[25] Gagliani N, Vesely MC, Iseppon A, Brockmann L, Xu H, Palm NW, de Zoete MR, Licona-Limón P, Paiva RS, Ching T, Weaver C, Zi X, Pan X, Fan R, Garmire LX, Cotton MJ, Drier Y, Bernstein B, Geginat J, Stockinger B, Esplugues E, Huber S, Flavell RA. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation[J]. Nature, 2015, 523:221-225.
[26] Jin WN, Gonzales R, Feng Y, Wood K, Chai Z, Dong JF, Cava AL, Shi FD, Liu Q. Brain ischemia induces diversified neuroantigen-specific T-cell responses that exacerbate brain injury[J]. Stroke, 2018, 49:1471-1478.

Please choose a citation manager

Content to export