Autoantigen and IL-2 activated CD4+CD25+T regulatory cells are induced to express CD8 and are autoantigen specific in inhibiting experimental autoimmune encephalomyelitis

被引：0

作者：

Tran, Giang T. ^{[1
]}

Bedi, Sukhandep ^{[1
]}

Rakesh, Prateek ^{[1
]}

Verma, Nirupama D. ^{[1
]}

Carter, Nicole ^{[1
,2
,3
]}

Robinson, Catherine M. ^{[1
,2
,3
]}

Al-Atiyah, Ranje ^{[1
,2
,3
]}

Hall, Bruce M. ^{[1
,3
]}

Hodgkinson, Suzanne J. ^{[1
,2
,3
]}

机构：

[1] UNSW Sydney, Ingham Inst, Immune Tolerance Lab, Fac Med, Liverpool, NSW, Australia

[2] Liverpool Hlth Serv, Dept Neurol, Liverpool, NSW, Australia

[3] Liverpool Hlth Serv, Dept Nephrol, Locked Bag 7017, Liverpool BC, NSW 1871, Australia

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2025年 / 404卷

关键词：

T regulatory cells; interleukin-2; autoimmunity; experimental autoimmune encephalomyelitis; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CD4+ SUPPRESSOR-CELLS; CARDIAC ALLOGRAFT SURVIVAL; CENTRAL-NERVOUS-SYSTEM; T-CELLS; EFFECTOR-CELLS; IFN-GAMMA; INTERFERON-GAMMA; IN-VITRO; ADOPTIVE TRANSFER;

D O I：

10.1016/j.jneuroim.2025.578611

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin basic protein (MBP) is a self-limiting disease model of multiple sclerosis. CD4+CD25+Foxp3+T cells play a role in limiting autoimmune disease but treatment with antigen na & iuml;ve CD4+CD25+ cells does not reduce EAE. This study examined if in vitro activation by MBP and rIL-2 induced CD4+CD25+Foxp3+ cells that could inhibit EAE. Culture of CD4+CD8-CD25+cells from na & iuml;ve rats with MBP and rIL-2 induced activated Treg that reduced the severity of clinical EAE and infiltration of CD8+T cells and macrophage into brain stem. CD4+CD25+T cells activated by an irrelevant autoantigen and rIL-2 did not suppress EAE. Resting CD4+CD25+T cells activated by autoantigen and rIL-2 have mRNA for Infgr, Il12rb2, Il5 but not Tbet, Gata3, Ilr5ra or Ifng. These changes in mRNA expression are the markers of Ts1 cells. A proportion of CD4+CD8-CD25+ cells activated by MBP/rIL-2 were induced to express CD8 alpha, CD8(3 and CD62L. Depletion of CD4+CD8 alpha+CD25+ cells removed the capacity of MBP and rIL-2 activated CD4+CD25+T cells to suppress EAE. This study demonstrated that in vitro activation of CD4+CD8-CD25+ cells by MBP/rIL-2 induced relevant antigen-specific Treg within days, which expressed CD8 alpha, CD8(3 and CD62L with a Ts1 phenotype and that had greater potency than freshly isolated antigen naive CD4+CD25+Treg in suppressing clinical severity of EAE and immune inflammation in CNS. These findings may guide development of antigen-specific Treg for therapy.

引用

页数：15

共 109 条

[1] EVIDENCE FOR SUPPRESSOR CELLS IN LEWIS RATS EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS [J].

ADDA, DH ;

BERAUD, E ;

DEPIEDS, R .

EUROPEAN JOURNAL OF IMMUNOLOGY, 1977, 7 (09) :620-623

[2] From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation [J].

Bacchetta, Rosa ;

Barzaghi, Federica ;

Roncarolo, Maria-Grazia .

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 2018, 1417 (01) :5-22

[3] DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells [J].

Baron, Udo ;

Floess, Stefan ;

Wieczorek, Georg ;

Baumann, Katrin ;

Gruetzkau, Andreas ;

Dong, Jun ;

Thiel, Andreas ;

Boeld, Tina J. ;

Hoffmann, Petra ;

Edinger, Matthias ;

Tuerbachova, Ivana ;

Hamann, Alf ;

Olek, Sven ;

Huehn, Jochen .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2007, 37 (09) :2378-2389

[4] Patients With Severe Multiple Sclerosis Exhibit Functionally Altered CD8+ Regulatory T Cells [J].

Benallegue, Nail ;

Nicol, Bryan ;

Lasselin, Juliette ;

Bezie, Severine ;

Flippe, Lea ;

Regue, Hadrien ;

Vimond, Nadege ;

Remy, Severine ;

Garcia, Alexandra ;

Le Frere, Fabienne ;

Anegon, Ignacio ;

Laplaud, David ;

Guillonneau, Carole .

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION, 2022, 9 (06)

[5] Antigen-specific splenic CD4+ and CD8+ regulatory T cells generated via the eye, suppress Experimental Autoimmune Encephalomyelitis either at the priming or at the effector phase [J].

Bhowmick, Sourojit ;

Clark, Robert B. ;

Brocke, Stefan ;

Cone, Robert E. .

INTERNATIONAL IMMUNOLOGY, 2011, 23 (02) :119-128

[6]

BILLIAU A, 1988, J IMMUNOL, V140, P1506

[7] Type 1 diabetes immunotherapy using polyclonal regulatory T cells [J].

Bluestone, Jeffrey A. ;

Buckner, Jane H. ;

Fitch, Mark ;

Gitelman, Stephen E. ;

Gupta, Shipra ;

Hellerstein, Marc K. ;

Herold, Kevan C. ;

Lares, Angela ;

Lee, Michael R. ;

Li, Kelvin ;

Liu, Weihong ;

Long, S. Alice ;

Masiello, Lisa M. ;

Vinh Nguyen ;

Putnam, Amy L. ;

Rieck, Mary ;

Sayre, Peter H. ;

Tang, Qizhi .

SCIENCE TRANSLATIONAL MEDICINE, 2015, 7 (315)

[8] Harnessing CD8+CD28- Regulatory T Cells as a Tool to Treat Autoimmune Disease [J].

Ceeraz, Sabrina ;

Thompson, Charlotte R. ;

Beatson, Richard ;

Choy, Ernest H. .

CELLS, 2021, 10 (11)

[9] Polyclonal Regulatory T Cell Therapy for Control of Inflammation in Kidney Transplants [J].

Chandran, S. ;

Tang, Q. ;

Sarwal, M. ;

Laszik, Z. G. ;

Putnam, A. L. ;

Lee, K. ;

Leung, J. ;

Nguyen, V. ;

Sigdel, T. ;

Tavares, E. C. ;

Yang, J. Y. C. ;

Hellerstein, M. ;

Fitch, M. ;

Bluestone, J. A. ;

Vincenti, F. .

AMERICAN JOURNAL OF TRANSPLANTATION, 2017, 17 (11) :2945-2954

[10] Novel CD8+ Treg suppress EAE by TGF-β- and IFN-γ-dependent mechanisms [J].

Chen, Mei-Ling ;

Yan, Bo-Shiun ;

Kozoriz, Deneen ;

Weiner, Howard L. .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2009, 39 (12) :3423-3435

← 1 2 3 4 5 6 7 8 9 10 →