DOI: 10.1084/jem.186.1.159. Treatment of Experimental Autoimmune Encephalomyelitis with Genetically Modified Memory T Cells

Treatment of Experimental Autoimmune Encephalomyelitis with Genetically Modified Memory T Cells

10.1084/jem.186.1.159

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

The migratory properties of memory T cells provide a model vector system for site-specific delivery of therapeutic transgene factors to autoimmune inflammatory lesions. Lymph node cells from (SWR×SJL)F1 mice immunized with the p139–151 determinant of myelin proteolipid protein (PLP) were transfected with a DNA construct that placed the anti-inflammatory cytokine interleukin-10 (IL-10) cDNA under control of an antigen-inducible IL-2 promoter region. Isolated T cell clones demonstrated antigen-inducible expression of transgene IL-10 and expressed cell surface markers consistent with the phenotype of normal memory T cells. Upon adoptive transfer, transfected T cell clones were able to inhibit onset of experimental autoimmune encephalomyelitis (EAE) and to treat EAE animals therapeutically after onset of neurologic signs. Semiquantitative immunocytochemistry showed a significant correlation between decreased demyelination and treatment with the transfected T cells. Taken together, these data indicate the autoreactive T cells can be genetically designed to produce therapeutic factors in an antigen-inducible manner resulting in a decreased severity of clinical and histological autoimmune demyelinating disease.

Bibliography

Mathisen, P. M., Yu, M., Johnson, J. M., Drazba, J. A., & Tuohy, V. K. (1997). Treatment of Experimental Autoimmune Encephalomyelitis with Genetically Modified Memory T Cells. The Journal of Experimental Medicine, 186(1), 159â164.

Authors 5

Peter M. Mathisen (first)
Min Yu (additional)
Justin M. Johnson (additional)
Judith A. Drazba (additional)
Vincent K. Tuohy (additional)

References 26 Referenced 145

10.1146/annurev.iy.10.040192.001101 / Annu Rev Immunol / Immunological aspects of demyelinating diseases by Martin (1992)
10.1016/S0092-8674(00)81107-1 / Cell / Multiple sclerosis: a coordinated immunological attack against myelin the central nervous system by Steinman (1996)
10.1212/WNL.30.7_Part_2.99 / Neurology / Multiple sclerosis: evidence for immunopathogenesis by Lisak (1980)
10.1056/NEJM198211043071905 / N Engl J Med / Multiple sclerosis (first of two parts) by McFarlin (1982)
10.1016/0092-8674(95)90349-6 / Cell / B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: applications to autoimmune disease therapy by Kuchroo (1995)
10.1084/jem.170.6.2081 / J Exp Med / Two types of mouse helper T cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones by Fiorentino (1989)
10.1126/science.2161559 / Science (Wash DC) / Homology of cytokine synthesis inhibitory factor (IL-10) to Epstein–Barr virus gene BCRFI by Moore (1990)
10.1073/pnas.88.4.1172 / Proc Natl Acad Sci USA / Isolation and expression of human cytokine synthesis inhibitory factor (CSIF/IL10) cDNA clones: homology to Epstein–Barr virus open reading frame BCRFI by Vieira (1991)
10.4049/jimmunol.149.7.2496 / J Immunol / Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery by Kennedy (1992)
10.1002/eji.1830240629 / Eur J Immunol / Interleukin-10 prevents experimental allergic encephalomyelitis in rats by Rott (1994)
10.1093/nar/18.15.4523 / Nucleic Acids Res / Regulatory anatomy of the murine interleukin-2 gene by Novak (1990)
10.1007/BF02821509 / Mol Biotech / Polybrene/DMSO-assisted gene transfer by Aubin (1994)
10.1093/nar/16.5.2352 / Nucleic Acids Res / Transfection of myeloid cell lines using polybrene/DMSO by Chisholm (1988)
10.1101/gad.1.10.1107 / Genes Dev / Thyroid hormone induction of keratin genes: a two-step activation of gene expression during development by Mathisen (1987)
10.1021/bi00591a005 / Biochemistry / Isolation of biologically active RNA from sources enriched in ribonucleases by Chirgwin (1979)
{'key': '2023072915173713400_B16', 'first-page': '532', 'article-title': 'A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples', 'volume': '15', 'author': 'Chomczynski', 'year': '1993', 'journal-title': 'BioTechniques'} / BioTechniques / A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples by Chomczynski (1993)
10.4049/jimmunol.142.5.1523 / J Immunol / Identification of an encephalitogenic determinant of myelin proteolipid protein for SJL mice by Tuohy (1989)
10.4049/jimmunol.156.6.2316 / J Immunol / Retrovirus-mediated transfer of viral IL-10 gene prolongs murine cardiac allograft survival by Qin (1996)
10.1002/eji.1830261020 / Eur J Immunol / Attenuation of collagen-induced arthritis in mice by treatment with vector cells engineered to secrete interleukin-13 by Bessis (1996)
10.1084/jem.179.4.1379 / J Exp Med / Production of interleukin 10 by islet cells accelerates immune-mediated destruction of β cells in nonobese diabetic mice by Wogensen (1994)
10.4049/jimmunol.155.10.5011 / J Immunol / Neuroantigen-specific Th2 cells are inefficient suppressors of experimental autoimmune encephalomyelitis induced effector Th1 cells by Khoruts (1995)
10.1016/0165-5728(93)90194-4 / J Neuroimmunol / Encephalitogenic Th1 cells are inhibited by Th2 cells with related peptide specificity: relative roles of interleukin (IL)-4 and IL-10 by van der Veen (1993)
10.1002/(SICI)1097-4547(19960915)45:6<735::AID-JNR10>3.0.CO;2-V / J Neurosci Res / IL-10 fails to abrogate experimental autoimmune encephalomyelitis by Cannella (1996)
10.1084/jem.185.9.1711 / J Exp Med / Local delivery of interleukin-4 by retrovirus-transduced lymphocytes ameliorates experimental autoimmune encephalomyelitis by Shaw (1997)
10.1038/nm1195-1162 / Nature Med / Gene transfer through the blood– nerve barrier: NGF-engineered neuritogenic T lymphocytes attenuate experimental autoimmune neuritis by Kramer (1995)
10.1016/0165-5728(94)00143-C / J Neuroimmunol / Sequence of 104– 117 of myelin proteolipid protein is a cryptic encephalitogenic T cell determinant for SJL/J mice by Tuohy (1995)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:49 p.m.)
Deposited	2 years, 1 month ago (July 29, 2023, 11:18 a.m.)
Indexed	1 month ago (Aug. 2, 2025, 12:31 a.m.)
Issued	28 years, 1 month ago (July 7, 1997)
Published	28 years, 1 month ago (July 7, 1997)
Published Online	28 years, 1 month ago (July 7, 1997)
Published Print	28 years, 1 month ago (July 7, 1997)

Funders 0

None

BibTeX

@article{Mathisen_1997, title={Treatment of Experimental Autoimmune Encephalomyelitis with Genetically Modified Memory T Cells}, volume={186}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.186.1.159}, DOI={10.1084/jem.186.1.159}, number={1}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Mathisen, Peter M. and Yu, Min and Johnson, Justin M. and Drazba, Judith A. and Tuohy, Vincent K.}, year={1997}, month=jul, pages={159–164} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        2
      ]
    ],
    "date-time": "2025-08-02T04:31:12Z",
    "timestamp": 1754109072190
  },
  "reference-count": 26,
  "publisher": "Rockefeller University Press",
  "issue": "1",
  "content-domain": {
    "domain": [
      "rupress.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        1997,
        7,
        7
      ]
    ]
  },
  "abstract": "<jats:p>The migratory properties of memory T cells provide a model vector system for site-specific delivery of therapeutic transgene factors to autoimmune inflammatory lesions. Lymph node cells from (SWR\u00d7SJL)F1 mice immunized with the p139\u2013151 determinant of myelin proteolipid protein (PLP) were transfected with a DNA construct that placed the anti-inflammatory cytokine interleukin-10 (IL-10) cDNA under control of an antigen-inducible IL-2 promoter region. Isolated T cell clones demonstrated antigen-inducible expression of transgene IL-10 and expressed cell surface markers consistent with the phenotype of normal memory T cells. Upon adoptive transfer, transfected T cell clones were able to inhibit onset of experimental autoimmune encephalomyelitis (EAE) and to treat EAE animals therapeutically after onset of neurologic signs. Semiquantitative immunocytochemistry showed a significant correlation between decreased demyelination and treatment with the transfected T cells. Taken together, these data indicate the autoreactive T cells can be genetically designed to produce therapeutic factors in an antigen-inducible manner resulting in a decreased severity of clinical and histological autoimmune demyelinating disease.</jats:p>",
  "DOI": "10.1084/jem.186.1.159",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T16:49:30Z",
    "timestamp": 1027702170000
  },
  "page": "159-164",
  "update-policy": "http://dx.doi.org/10.1084/jem.crossmarkpolicy",
  "source": "Crossref",
  "is-referenced-by-count": 145,
  "title": "Treatment of Experimental Autoimmune Encephalomyelitis with Genetically Modified Memory T Cells",
  "prefix": "10.1084",
  "volume": "186",
  "author": [
    {
      "given": "Peter M.",
      "family": "Mathisen",
      "sequence": "first",
      "affiliation": [
        {
          "name": "From *The Cleveland Clinic Foundation, Research Institute, Department of Immunology, FFb-1, and \u2021The Cleveland Clinic Confocal Core Facility, Cleveland, Ohio 44195"
        }
      ]
    },
    {
      "given": "Min",
      "family": "Yu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From *The Cleveland Clinic Foundation, Research Institute, Department of Immunology, FFb-1, and \u2021The Cleveland Clinic Confocal Core Facility, Cleveland, Ohio 44195"
        }
      ]
    },
    {
      "given": "Justin M.",
      "family": "Johnson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From *The Cleveland Clinic Foundation, Research Institute, Department of Immunology, FFb-1, and \u2021The Cleveland Clinic Confocal Core Facility, Cleveland, Ohio 44195"
        }
      ]
    },
    {
      "given": "Judith A.",
      "family": "Drazba",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From *The Cleveland Clinic Foundation, Research Institute, Department of Immunology, FFb-1, and \u2021The Cleveland Clinic Confocal Core Facility, Cleveland, Ohio 44195"
        }
      ]
    },
    {
      "given": "Vincent K.",
      "family": "Tuohy",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From *The Cleveland Clinic Foundation, Research Institute, Department of Immunology, FFb-1, and \u2021The Cleveland Clinic Confocal Core Facility, Cleveland, Ohio 44195"
        }
      ]
    }
  ],
  "member": "291",
  "published-online": {
    "date-parts": [
      [
        1997,
        7,
        7
      ]
    ]
  },
  "reference": [
    {
      "key": "2023072915173713400_B1",
      "doi-asserted-by": "crossref",
      "first-page": "153",
      "DOI": "10.1146/annurev.iy.10.040192.001101",
      "article-title": "Immunological aspects of demyelinating diseases",
      "volume": "10",
      "author": "Martin",
      "year": "1992",
      "journal-title": "Annu Rev Immunol"
    },
    {
      "key": "2023072915173713400_B2",
      "doi-asserted-by": "crossref",
      "first-page": "299",
      "DOI": "10.1016/S0092-8674(00)81107-1",
      "article-title": "Multiple sclerosis: a coordinated immunological attack against myelin the central nervous system",
      "volume": "85",
      "author": "Steinman",
      "year": "1996",
      "journal-title": "Cell"
    },
    {
      "key": "2023072915173713400_B3",
      "doi-asserted-by": "crossref",
      "first-page": "99",
      "DOI": "10.1212/WNL.30.7_Part_2.99",
      "article-title": "Multiple sclerosis: evidence for immunopathogenesis",
      "volume": "30",
      "author": "Lisak",
      "year": "1980",
      "journal-title": "Neurology"
    },
    {
      "key": "2023072915173713400_B4",
      "doi-asserted-by": "crossref",
      "first-page": "1183",
      "DOI": "10.1056/NEJM198211043071905",
      "article-title": "Multiple sclerosis (first of two parts)",
      "volume": "307",
      "author": "McFarlin",
      "year": "1982",
      "journal-title": "N Engl J Med"
    },
    {
      "key": "2023072915173713400_B5",
      "doi-asserted-by": "crossref",
      "first-page": "707",
      "DOI": "10.1016/0092-8674(95)90349-6",
      "article-title": "B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: applications to autoimmune disease therapy",
      "volume": "80",
      "author": "Kuchroo",
      "year": "1995",
      "journal-title": "Cell"
    },
    {
      "key": "2023072915173713400_B6",
      "doi-asserted-by": "crossref",
      "first-page": "2081",
      "DOI": "10.1084/jem.170.6.2081",
      "article-title": "Two types of mouse helper T cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones",
      "volume": "170",
      "author": "Fiorentino",
      "year": "1989",
      "journal-title": "J Exp Med"
    },
    {
      "key": "2023072915173713400_B7",
      "doi-asserted-by": "crossref",
      "first-page": "1230",
      "DOI": "10.1126/science.2161559",
      "article-title": "Homology of cytokine synthesis inhibitory factor (IL-10) to Epstein\u2013Barr virus gene BCRFI",
      "volume": "24",
      "author": "Moore",
      "year": "1990",
      "journal-title": "Science (Wash DC)"
    },
    {
      "key": "2023072915173713400_B8",
      "doi-asserted-by": "crossref",
      "first-page": "1172",
      "DOI": "10.1073/pnas.88.4.1172",
      "article-title": "Isolation and expression of human cytokine synthesis inhibitory factor (CSIF/IL10) cDNA clones: homology to Epstein\u2013Barr virus open reading frame BCRFI",
      "volume": "88",
      "author": "Vieira",
      "year": "1991",
      "journal-title": "Proc Natl Acad Sci USA"
    },
    {
      "key": "2023072915173713400_B9",
      "doi-asserted-by": "crossref",
      "first-page": "2496",
      "DOI": "10.4049/jimmunol.149.7.2496",
      "article-title": "Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery",
      "volume": "149",
      "author": "Kennedy",
      "year": "1992",
      "journal-title": "J Immunol"
    },
    {
      "key": "2023072915173713400_B10",
      "doi-asserted-by": "crossref",
      "first-page": "1434",
      "DOI": "10.1002/eji.1830240629",
      "article-title": "Interleukin-10 prevents experimental allergic encephalomyelitis in rats",
      "volume": "24",
      "author": "Rott",
      "year": "1994",
      "journal-title": "Eur J Immunol"
    },
    {
      "key": "2023072915173713400_B11",
      "doi-asserted-by": "crossref",
      "first-page": "4523",
      "DOI": "10.1093/nar/18.15.4523",
      "article-title": "Regulatory anatomy of the murine interleukin-2 gene",
      "volume": "18",
      "author": "Novak",
      "year": "1990",
      "journal-title": "Nucleic Acids Res"
    },
    {
      "key": "2023072915173713400_B12",
      "doi-asserted-by": "crossref",
      "first-page": "29",
      "DOI": "10.1007/BF02821509",
      "article-title": "Polybrene/DMSO-assisted gene transfer",
      "volume": "1",
      "author": "Aubin",
      "year": "1994",
      "journal-title": "Mol Biotech"
    },
    {
      "key": "2023072915173713400_B13",
      "doi-asserted-by": "crossref",
      "first-page": "23523",
      "DOI": "10.1093/nar/16.5.2352",
      "article-title": "Transfection of myeloid cell lines using polybrene/DMSO",
      "volume": "16",
      "author": "Chisholm",
      "year": "1988",
      "journal-title": "Nucleic Acids Res"
    },
    {
      "key": "2023072915173713400_B14",
      "doi-asserted-by": "crossref",
      "first-page": "1107",
      "DOI": "10.1101/gad.1.10.1107",
      "article-title": "Thyroid hormone induction of keratin genes: a two-step activation of gene expression during development",
      "volume": "1",
      "author": "Mathisen",
      "year": "1987",
      "journal-title": "Genes Dev"
    },
    {
      "key": "2023072915173713400_B15",
      "doi-asserted-by": "crossref",
      "first-page": "5294",
      "DOI": "10.1021/bi00591a005",
      "article-title": "Isolation of biologically active RNA from sources enriched in ribonucleases",
      "volume": "18",
      "author": "Chirgwin",
      "year": "1979",
      "journal-title": "Biochemistry"
    },
    {
      "key": "2023072915173713400_B16",
      "first-page": "532",
      "article-title": "A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples",
      "volume": "15",
      "author": "Chomczynski",
      "year": "1993",
      "journal-title": "BioTechniques"
    },
    {
      "key": "2023072915173713400_B17",
      "doi-asserted-by": "crossref",
      "first-page": "1523",
      "DOI": "10.4049/jimmunol.142.5.1523",
      "article-title": "Identification of an encephalitogenic determinant of myelin proteolipid protein for SJL mice",
      "volume": "142",
      "author": "Tuohy",
      "year": "1989",
      "journal-title": "J Immunol"
    },
    {
      "key": "2023072915173713400_B18",
      "doi-asserted-by": "crossref",
      "first-page": "2316",
      "DOI": "10.4049/jimmunol.156.6.2316",
      "article-title": "Retrovirus-mediated transfer of viral IL-10 gene prolongs murine cardiac allograft survival",
      "volume": "156",
      "author": "Qin",
      "year": "1996",
      "journal-title": "J Immunol"
    },
    {
      "key": "2023072915173713400_B19",
      "doi-asserted-by": "crossref",
      "first-page": "2399",
      "DOI": "10.1002/eji.1830261020",
      "article-title": "Attenuation of collagen-induced arthritis in mice by treatment with vector cells engineered to secrete interleukin-13",
      "volume": "26",
      "author": "Bessis",
      "year": "1996",
      "journal-title": "Eur J Immunol"
    },
    {
      "key": "2023072915173713400_B20",
      "doi-asserted-by": "crossref",
      "first-page": "1379",
      "DOI": "10.1084/jem.179.4.1379",
      "article-title": "Production of interleukin 10 by islet cells accelerates immune-mediated destruction of \u03b2 cells in nonobese diabetic mice",
      "volume": "179",
      "author": "Wogensen",
      "year": "1994",
      "journal-title": "J Exp Med"
    },
    {
      "key": "2023072915173713400_B21",
      "doi-asserted-by": "crossref",
      "first-page": "5011",
      "DOI": "10.4049/jimmunol.155.10.5011",
      "article-title": "Neuroantigen-specific Th2 cells are inefficient suppressors of experimental autoimmune encephalomyelitis induced effector Th1 cells",
      "volume": "155",
      "author": "Khoruts",
      "year": "1995",
      "journal-title": "J Immunol"
    },
    {
      "key": "2023072915173713400_B22",
      "doi-asserted-by": "crossref",
      "first-page": "213",
      "DOI": "10.1016/0165-5728(93)90194-4",
      "article-title": "Encephalitogenic Th1 cells are inhibited by Th2 cells with related peptide specificity: relative roles of interleukin (IL)-4 and IL-10",
      "volume": "48",
      "author": "van der Veen",
      "year": "1993",
      "journal-title": "J Neuroimmunol"
    },
    {
      "key": "2023072915173713400_B23",
      "doi-asserted-by": "crossref",
      "first-page": "735",
      "DOI": "10.1002/(SICI)1097-4547(19960915)45:6<735::AID-JNR10>3.0.CO;2-V",
      "article-title": "IL-10 fails to abrogate experimental autoimmune encephalomyelitis",
      "volume": "45",
      "author": "Cannella",
      "year": "1996",
      "journal-title": "J Neurosci Res"
    },
    {
      "key": "2023072915173713400_B24",
      "doi-asserted-by": "crossref",
      "first-page": "1541",
      "DOI": "10.1084/jem.185.9.1711",
      "article-title": "Local delivery of interleukin-4 by retrovirus-transduced lymphocytes ameliorates experimental autoimmune encephalomyelitis",
      "volume": "185",
      "author": "Shaw",
      "year": "1997",
      "journal-title": "J Exp Med"
    },
    {
      "key": "2023072915173713400_B25",
      "doi-asserted-by": "crossref",
      "first-page": "1162",
      "DOI": "10.1038/nm1195-1162",
      "article-title": "Gene transfer through the blood\u2013 nerve barrier: NGF-engineered neuritogenic T lymphocytes attenuate experimental autoimmune neuritis",
      "volume": "1",
      "author": "Kramer",
      "year": "1995",
      "journal-title": "Nature Med"
    },
    {
      "key": "2023072915173713400_B26",
      "doi-asserted-by": "crossref",
      "first-page": "161",
      "DOI": "10.1016/0165-5728(94)00143-C",
      "article-title": "Sequence of 104\u2013 117 of myelin proteolipid protein is a cryptic encephalitogenic T cell determinant for SJL/J mice",
      "volume": "56",
      "author": "Tuohy",
      "year": "1995",
      "journal-title": "J Neuroimmunol"
    }
  ],
  "container-title": "The Journal of Experimental Medicine",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://rupress.org/jem/article-pdf/186/1/159/1896539/97-0214.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://rupress.org/jem/article-pdf/186/1/159/1896539/97-0214.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        7,
        29
      ]
    ],
    "date-time": "2023-07-29T15:18:02Z",
    "timestamp": 1690643882000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://rupress.org/jem/article/186/1/159/7188/Treatment-of-Experimental-Autoimmune"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1997,
        7,
        7
      ]
    ]
  },
  "references-count": 26,
  "journal-issue": {
    "issue": "1",
    "published-print": {
      "date-parts": [
        [
          1997,
          7,
          7
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1084/jem.186.1.159",
  "relation": {},
  "ISSN": [
    "0022-1007",
    "1540-9538"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        1997,
        7,
        7
      ]
    ]
  }
}