In trans T cell tolerance diminishes autoantibody responses and exacerbates experimental allergic encephalomyelitis

J. Jeremiah Bell, Rohit D. Divekar, Jason S. Ellis, Jason A. Cascio, Cara L. Haymaker, Renu Jain, Danielle Tartar, Christine M. Hoeman, John C. Hardaway, Habib Zaghouani

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

A number of Ag-specific approaches have been developed that ameliorate experimental allergic encephalomyelitis (EAE), an animal model for the human autoimmune disease multiple sclerosis. Translation to humans, however, remains a consideration, justifying the search for more insight into the mechanism underlying restoration of self-tolerance. Ig-proteolipid protein (PLP) 1 and Ig-myelin oligodendrocyte glycoprotein (MOG) are Ig chimeras carrying the encephalitogenic PLP 139-151 and MOG 35-55 amino acid sequence, respectively. Ig-PLP1 ameliorates EAE in SJL/J (H-2s) mice while Ig-MOG modulates the disease in C57BL/6 (H-2b) animals. In this study, we asked whether the chimeras would suppress EAE in F1 mice expressing both parental MHC alleles and representing a polymorphism with more relevance to human circumstances. The results show that Ig-MOG modulates both PLP1 and MOG peptide-induced EAE in the F1 mice, whereas Ig-PLP1 counters PLP1 EAE but exacerbates MOG-induced disease. This in trans aggravation of MOG EAE by Ig-PLP1 operates through induction of PLP1-specific T cells producing IL-5 that sustained inhibition of MOG-specific Abs leading to exacerbation of EAE. Thus, in trans T cell tolerance, which should be operative in polymorphic systems, can aggravate rather than ameliorate autoimmunity. This phenomenon possibly takes place through interference with protective humoral immunity.

Original languageEnglish (US)
Pages (from-to)1508-1516
Number of pages9
JournalJournal of Immunology
Volume180
Issue number3
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

Fingerprint

Myelin-Oligodendrocyte Glycoprotein
Autoimmune Experimental Encephalomyelitis
Autoantibodies
T-Lymphocytes
Proteolipids
Self Tolerance
Interleukin-5
Humoral Immunity
Autoimmunity
Autoimmune Diseases
Multiple Sclerosis
Amino Acid Sequence
Animal Models
Alleles
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

Bell, J. J., Divekar, R. D., Ellis, J. S., Cascio, J. A., Haymaker, C. L., Jain, R., ... Zaghouani, H. (2008). In trans T cell tolerance diminishes autoantibody responses and exacerbates experimental allergic encephalomyelitis. Journal of Immunology, 180(3), 1508-1516. https://doi.org/10.4049/jimmunol.180.3.1508

In trans T cell tolerance diminishes autoantibody responses and exacerbates experimental allergic encephalomyelitis. / Bell, J. Jeremiah; Divekar, Rohit D.; Ellis, Jason S.; Cascio, Jason A.; Haymaker, Cara L.; Jain, Renu; Tartar, Danielle; Hoeman, Christine M.; Hardaway, John C.; Zaghouani, Habib.

In: Journal of Immunology, Vol. 180, No. 3, 01.02.2008, p. 1508-1516.

Research output: Contribution to journalArticle

Bell, JJ, Divekar, RD, Ellis, JS, Cascio, JA, Haymaker, CL, Jain, R, Tartar, D, Hoeman, CM, Hardaway, JC & Zaghouani, H 2008, 'In trans T cell tolerance diminishes autoantibody responses and exacerbates experimental allergic encephalomyelitis', Journal of Immunology, vol. 180, no. 3, pp. 1508-1516. https://doi.org/10.4049/jimmunol.180.3.1508
Bell, J. Jeremiah ; Divekar, Rohit D. ; Ellis, Jason S. ; Cascio, Jason A. ; Haymaker, Cara L. ; Jain, Renu ; Tartar, Danielle ; Hoeman, Christine M. ; Hardaway, John C. ; Zaghouani, Habib. / In trans T cell tolerance diminishes autoantibody responses and exacerbates experimental allergic encephalomyelitis. In: Journal of Immunology. 2008 ; Vol. 180, No. 3. pp. 1508-1516.
@article{ab420d99b8fe429ebc3d12acc58aa93e,
title = "In trans T cell tolerance diminishes autoantibody responses and exacerbates experimental allergic encephalomyelitis",
abstract = "A number of Ag-specific approaches have been developed that ameliorate experimental allergic encephalomyelitis (EAE), an animal model for the human autoimmune disease multiple sclerosis. Translation to humans, however, remains a consideration, justifying the search for more insight into the mechanism underlying restoration of self-tolerance. Ig-proteolipid protein (PLP) 1 and Ig-myelin oligodendrocyte glycoprotein (MOG) are Ig chimeras carrying the encephalitogenic PLP 139-151 and MOG 35-55 amino acid sequence, respectively. Ig-PLP1 ameliorates EAE in SJL/J (H-2s) mice while Ig-MOG modulates the disease in C57BL/6 (H-2b) animals. In this study, we asked whether the chimeras would suppress EAE in F1 mice expressing both parental MHC alleles and representing a polymorphism with more relevance to human circumstances. The results show that Ig-MOG modulates both PLP1 and MOG peptide-induced EAE in the F1 mice, whereas Ig-PLP1 counters PLP1 EAE but exacerbates MOG-induced disease. This in trans aggravation of MOG EAE by Ig-PLP1 operates through induction of PLP1-specific T cells producing IL-5 that sustained inhibition of MOG-specific Abs leading to exacerbation of EAE. Thus, in trans T cell tolerance, which should be operative in polymorphic systems, can aggravate rather than ameliorate autoimmunity. This phenomenon possibly takes place through interference with protective humoral immunity.",
author = "Bell, {J. Jeremiah} and Divekar, {Rohit D.} and Ellis, {Jason S.} and Cascio, {Jason A.} and Haymaker, {Cara L.} and Renu Jain and Danielle Tartar and Hoeman, {Christine M.} and Hardaway, {John C.} and Habib Zaghouani",
year = "2008",
month = "2",
day = "1",
doi = "10.4049/jimmunol.180.3.1508",
language = "English (US)",
volume = "180",
pages = "1508--1516",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - In trans T cell tolerance diminishes autoantibody responses and exacerbates experimental allergic encephalomyelitis

AU - Bell, J. Jeremiah

AU - Divekar, Rohit D.

AU - Ellis, Jason S.

AU - Cascio, Jason A.

AU - Haymaker, Cara L.

AU - Jain, Renu

AU - Tartar, Danielle

AU - Hoeman, Christine M.

AU - Hardaway, John C.

AU - Zaghouani, Habib

PY - 2008/2/1

Y1 - 2008/2/1

N2 - A number of Ag-specific approaches have been developed that ameliorate experimental allergic encephalomyelitis (EAE), an animal model for the human autoimmune disease multiple sclerosis. Translation to humans, however, remains a consideration, justifying the search for more insight into the mechanism underlying restoration of self-tolerance. Ig-proteolipid protein (PLP) 1 and Ig-myelin oligodendrocyte glycoprotein (MOG) are Ig chimeras carrying the encephalitogenic PLP 139-151 and MOG 35-55 amino acid sequence, respectively. Ig-PLP1 ameliorates EAE in SJL/J (H-2s) mice while Ig-MOG modulates the disease in C57BL/6 (H-2b) animals. In this study, we asked whether the chimeras would suppress EAE in F1 mice expressing both parental MHC alleles and representing a polymorphism with more relevance to human circumstances. The results show that Ig-MOG modulates both PLP1 and MOG peptide-induced EAE in the F1 mice, whereas Ig-PLP1 counters PLP1 EAE but exacerbates MOG-induced disease. This in trans aggravation of MOG EAE by Ig-PLP1 operates through induction of PLP1-specific T cells producing IL-5 that sustained inhibition of MOG-specific Abs leading to exacerbation of EAE. Thus, in trans T cell tolerance, which should be operative in polymorphic systems, can aggravate rather than ameliorate autoimmunity. This phenomenon possibly takes place through interference with protective humoral immunity.

AB - A number of Ag-specific approaches have been developed that ameliorate experimental allergic encephalomyelitis (EAE), an animal model for the human autoimmune disease multiple sclerosis. Translation to humans, however, remains a consideration, justifying the search for more insight into the mechanism underlying restoration of self-tolerance. Ig-proteolipid protein (PLP) 1 and Ig-myelin oligodendrocyte glycoprotein (MOG) are Ig chimeras carrying the encephalitogenic PLP 139-151 and MOG 35-55 amino acid sequence, respectively. Ig-PLP1 ameliorates EAE in SJL/J (H-2s) mice while Ig-MOG modulates the disease in C57BL/6 (H-2b) animals. In this study, we asked whether the chimeras would suppress EAE in F1 mice expressing both parental MHC alleles and representing a polymorphism with more relevance to human circumstances. The results show that Ig-MOG modulates both PLP1 and MOG peptide-induced EAE in the F1 mice, whereas Ig-PLP1 counters PLP1 EAE but exacerbates MOG-induced disease. This in trans aggravation of MOG EAE by Ig-PLP1 operates through induction of PLP1-specific T cells producing IL-5 that sustained inhibition of MOG-specific Abs leading to exacerbation of EAE. Thus, in trans T cell tolerance, which should be operative in polymorphic systems, can aggravate rather than ameliorate autoimmunity. This phenomenon possibly takes place through interference with protective humoral immunity.

UR - http://www.scopus.com/inward/record.url?scp=40749117207&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40749117207&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.180.3.1508

DO - 10.4049/jimmunol.180.3.1508

M3 - Article

C2 - 18209046

AN - SCOPUS:40749117207

VL - 180

SP - 1508

EP - 1516

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -