Identification and characteristics of a novel CD8αα T cell subset in a refractory myasthenia gravis patient

被引：0
作者：
Liu, Yujia [1 ]
Sun, Hanxiao [2 ]
Xu, Yingchen [3 ]
Xuan, Binbin [2 ]
Xia, Guofang [4 ]
Tang, Jifeng [2 ]
Lin, Jinpiao [2 ]
Du, Ailian [5 ]
Sheng, Huiming [2 ]
机构：
[1] Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Dept Neurol, Shanghai 200336, Peoples R China
[2] Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Dept Lab Med, Shanghai 200336, Peoples R China
[3] Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China
[4] Shanghai Jiao Tong Univ, Peoples Hosp 6, Sch Med Affiliated, Dept Cardiol, Shanghai 200233, Peoples R China
[5] Shanghai Jiao Tong Univ, Songjiang Hosp, Sch Med, Dept Neurol, Shanghai 201699, Peoples R China
来源：
JOURNAL OF NEUROIMMUNOLOGY | 2025年 / 400卷
关键词：
CD8 alpha alpha T cell; CD161 neg T cell; MAIT cell; Myasthenia gravis; Thymoma; RECEPTOR; THYMOMA;
D O I：
10.1016/j.jneuroim.2025.578551
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Myasthenia gravis (MG) is an autoimmune disease that impairs neuromuscular transmission. Autoantibodies and cellular immunity mediate the immunopathology of MG, yet the mechanism of CD8+ T cells in this process remains elucidated. In this study, we discovered a novel subset of CD8 alpha alpha+ T cells in the peripheral blood of an 18-year-old Chinese man diagnosed as MG, who has undergone thymectomy and persistent myasthenia crisis. Designated as CD161neg T cell, this subset was characterized by TCR alpha beta+CD8 alpha alpha+PLZF+V alpha 7.2+ but notably lacked CD161, distinct from mucosal-associated invariant T (MAIT) cells known for high CD161. The patient exhibited unusually high levels of CD161neg T cells compared to other MG patients, which fluctuated with infections but not MG severity. RNA sequencing revealed that CD161neg T cells lacked the genes characteristic of mature MAIT cells including CCR6, CXCR6, ZBTB16, and IL18RAP, but expressed cytotoxic T cell-related genes GZMH and IFNG. This study shed new light on the heterogeneity and complexity of CD8 alpha alpha+ T cells in MG patients with thymoma.
引用
收藏
页数：9
相关论文
共 38 条
  • [21] Koay H.F., Su S., Amann-Zalcenstein D., Daley S.R., Comerford I., Miosge L., Whyte C.E., Konstantinov I.E., D'udekem Y., Baldwin T., Hickey P.F., Berzins S.P., Mak J.Y.W., Sontani Y., Roots C.M., Sidwell T., Kallies A., Chen Z., Nussing S., Kedzierska K., Mackay L.K., Mccoll S.R., Deenick E.K., Fairlie D.P., Mccluskey J., Goodnow C.C., Ritchie M.E., Belz G.T., Naik S.H., Pellicci D.G., Godfrey D.I., A divergent transcriptional landscape underpins the development and functional branching of MAIT
  • [22] Legoux F., Salou M., Lantz O., MAIT cell development and functions: The microbial connection, Immunity, 53, 4, pp. 710-723, (2020)
  • [23] Liu H., Fang W., Gu., Z., Recent advances in post-operatively new onset myasthenia gravis in thymoma patients, Cancer Res. Prevent. Treatment., 50, 10, pp. 941-945, (2023)
  • [24] Okamura T., Hamaguchi M., Tominaga H., Kitagawa N., Hashimoto Y., Majima S., Senmaru T., Okada H., Ushigome E., Nakanishi N., Shichino S., Fukui M., Characterization of peripheral blood TCR in patients with type 1 diabetes mellitus by BD Rhapsody(TM) VDJ CDR3 assay, Cells, 11, 10, (2022)
  • [25] Palmieri G., Selleri C., Montella L., Bulgarelli G., Vitiello L., Merkabaoui G., Ricci P., Del Vecchio L., Masci A., Racioppi L., Rotoli B., Thymoma followed by paroxysmal nocturnal hemoglobinuria: a unique clinical association in the context of multiorgan autoimmunity with a potential role for CD8+ T lymphocytes, Am. J. Hematol., 81, 10, pp. 774-778, (2006)
  • [26] Park D., Kim H.G., Kim M., Park T., Ha H.H., Lee D.H., Park K.S., Park S.J., Lim H.J., Lee C.H., Differences in the molecular signatures of mucosal-associated invariant T cells and conventional T cells, Sci. Rep., 9, 1, (2019)
  • [27] Peng Y., Yang H., Chen Q., Jin H., Xue Y.H., Du M.Q., Liu S., Yao S.Y., An angel or a devil? Current view on the role of CD8(+) T cells in the pathogenesis of myasthenia gravis, J. Transl. Med., 22, 1, (2024)
  • [28] Rao J., Li S., Wang X., Cheng Q., Ji Y., Fu W., Huang H., Shi L., Wu X., Comparison of peripheral blood regulatory T cells and functional subsets between ocular and generalized myasthenia gravis, Front Med (Lausanne)., 9, (2022)
  • [29] Sheng H., Marrero I., Maricic I., Fanchiang S.S., Zhang S., Sant'angelo D.B., Kumar V., Distinct PLZF(+)CD8αα(+) unconventional T cells enriched in liver use a cytotoxic mechanism to limit autoimmunity, J. Immunol., 203, 8, pp. 2150-2162, (2019)
  • [30] Singh P., Gaspar K., Szegedi A., Sajtos L., Barath S., Hevessy Z., Investigating vα7.2(+)/CD161(−) t cell and MAIT cell profiles using flow cytometry in healthy subjects and subjects with atopic dermatitis, Int. J. Mol. Sci., 25, 6, (2024)
1234