A Study of the Chemical Nature of Components of Bovine White Matter Effective in Producing Allergic Encephalomyelitis in the Rabbit

Waksman, Byron H.; Porter, Huntington; Lees, Marjorie B.; Adams, Raymond D.; Folch, Jordi

doi:10.1084/jem.100.5.451

Cited by 112 publications

(25 citation statements)

References 24 publications

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“…The other important putative autoantigen in MS is PLP due to its experimental encephalitogenicity (3,4). No significant T cell reactivity in MS with this antigen has previously been found (9,10).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Olsson¹,

Zhi²,

Höjeberg³

et al. 1990

J. Clin. Invest.

345

160

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Multiple sclerosis (MS) is a disease with unknown cause characterized by inflammation and demyelination in the central nervous system. Although an autoimmune pathogenesis has been suggested, there are no conclusive data on the number of T cells autoreactive with myelin antigens in MS compared to controls. We showed that T lymphocytes secreting interferony in response to possible target autoantigens are severalfold more common among PBL mononuclear cells in patients with MS than in patients with aseptic meningitis and tension headache. On average T cells reactive with myelin basic protein (MBP), two different MBP peptides, or with proteolipid protein amounted to 2.7-5.2/105 PBL from MS patients. MBPreactive T cells were still more frequent among mononuclear cells isolated from the cerebrospinal fluid (CSF; 185/10O CSF cells). We concluded that T cells reactive with myelin autoantigens are strongly increased in MS. This approach to detect them could allow definition of immunodominant T cell epitopes in individual MS patients, and thereby enable further development towards specific immunotherapy. (J. Clin. Invest. 1990. 86:981-985.)

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Section: Discussionmentioning

confidence: 99%

“…Induction of EAE depends on CD4' T cells that are autoreactive with myelin proteins (1). Myelin basic protein (MBP) (2) and proteolipid protein (PLP) (3,4) have both been shown to be encephalitogenic. Previous data on T cell reactivities to myelin antigens in MS (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) are partly inconsistent.…”

Section: Introductionmentioning

confidence: 99%

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Olsson¹,

Zhi²,

Höjeberg³

et al. 1990

J. Clin. Invest.

345

160

View full text Add to dashboard Cite

show abstract

“…Experimental autoimmune encephalomyelitis (EAE) can be induced by injection of MBP or PLP together with Freund's complete adjuvant (28)(29)(30), and represents to a certain extent an experimental model of multiple sclerosis. With the same T cell immunospot assay as used in the present study, we have documented that patients with multiple sclerosis have high numbers ofMBP-and PLP-reactive T cells in peripheral blood and especially in cerebrospinal fluid, i.e., in the compartment in the immediate vicinity of the target for a possible immune attack (16).…”

Section: Discussionmentioning

confidence: 99%

Acetylcholine receptor-reactive T and B cells in myasthenia gravis and controls.

Link¹,

Olsson²,

Sun³

et al. 1991

J. Clin. Invest.

112

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Myasthenia gravis (MG) is strongly associated with antibodies to acetylcholine receptor (AChR), whereas the extent of T cell involvement is not settled. The number of cells secreting interferon-gamma (IFN-'y) in response to AChR during 48 h culture of blood mononuclear cells (PBL) may reflect AChR-reactive T cells. Using an immunospot assay, we detected such cells in 23 of 30 patients with MG at a mean number of 1 per 33.333 PBL. AChR-reactive T cells were also found in patients with other neurological diseases (OND) and in healthy subjects but at lower frequencies and numbers. The T cell response to purified protein derivative and to PHA, and also to two major myelin proteins (basic protein and proteolipid protein) did not differ between MG and the two control groups, underlining the specificity ofan augmented T cell reactivity to AChR in MG. Evaluation of the B cell response by enumerating anti-AChR IgG antibody secreting cells revealed such cells in 27 of 28 patients with MG at a mean value of 1 per 14,085 PBL. Cells secreting anti-AChR antibodies of the IgA and IgM isotypes were also detected in MG, but less frequently, at lower numbers, and only in conjunction with IgG antibody secreting cells. Anti-AChR antibody secreting cells were also found among patient with OND and in healthy controls, but at lower frequencies and numbers. These data confirm that AChR is a major target for autoimmune response in MG. (J. Clin. Invest. 1991. 87:2191-2196

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“…In animal models, when such responses have been generated that target tumor-derived antigens that are shared with host cells, severe or at least clinically significant autoimmune disease has resulted [63,68,69]. In light of the documented expression of normal adult and fetal brain antigens on human glioma cell lines [70] and fresh tumor tissue [71][72][73][74], active immunization with unselected antigens risks inducing an uncontrolled autoimmune response against the normal central nervous system (CNS) similar to experimental allergic encephalomyelitis (EAE).Myelin basic protein (MBP) is the most common known antigenic trigger, but myelin proteolipid protein [75,76] The susceptibility of humans to the induction of EAE was discovered accidentally when patients were vaccinated against rabies with spinal cords from rabbits that were infected with the rabies virus [80][81][82][83][84]. Some concern regarding EAE is also warranted on the basis of previous active, specific immunotherapy trials in humans with brain tumors.…”

mentioning

confidence: 99%

Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma

Sampson

Archer

Mitchell

et al. 2008

Seminars in Immunology

154

131

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Conventional therapies for malignant gliomas (MGs) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by non-specific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication of neoplastic cells.The epidermal growth factor receptor variant III (EGFRvIII) is a consistent tumor-specific mutation that is widely expressed in MGs and other neoplasms. This mutation encodes a constitutively active tyrosine kinase that enhances tumorgenicity and migration and confers radiation and chemotherapeutic resistance. This in-frame deletion mutation splits a codon resulting in the creation of a novel glycine at the fusion junction between normally distant parts of the molecule and producing a sequence rearrangement which creates a tumor-specific epitope for cellular or humoral immunotherapy in patients with MGs.We have previously shown that vaccination with a peptide that spans the EGFRvIII fusion junction is an efficacious immunotherapy in syngeneic murine models, but patients with MGs have a profound immunosuppression that may inhibit the ability of antigen presenting cells (APCs), even those generated ex vivo, to induce EGFRvIII-specific immune responses. In this report, we summarize our results in humans targeting this mutation in two consecutive and one multi-institutional Phase II immunotherapy trials. These trials demonstrated that vaccines targeting EGFRvIII are capable of inducing potent T-and B-cell immunity in these patients, and an unexpectedly long survival time. Most importantly, vaccines targeting EGFRvIII were universally successful at eliminating tumor cells expressing the targeted antigen without any evidence of symptomatic collateral toxicity.These studies establish the tumor-specific EGFRvIII mutation as a novel target for humoral-and cell-mediated immunotherapy in a variety of cancers. The recurrence of EGFRvIII-negative tumors in our patients, however, highlights the need for targeting a broader repertoire of tumor-specific antigens. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. , and patients with recurrent tumors usually survive <20 weeks [7]. Moreover, the non-specific nature of conventional therapy for brain tumors often results in incapacitating damage to surrounding normal brain and systemic tissues [8]. Thus, in order to be more effective, therapeutic strategies will have to precisely target tumor cells while minimizing collateral damage to neighboring eloquent cerebral cortex. The rationale for employing the immune system to target brain tumors is based on the p...

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A Study of the Chemical Nature of Components of Bovine White Matter Effective in Producing Allergic Encephalomyelitis in the Rabbit

Cited by 112 publications

References 24 publications

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma.

Acetylcholine receptor-reactive T and B cells in myasthenia gravis and controls.

Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma

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