Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis

Research output: Contribution to journalArticle

B. E. Theien, C. L. Vanderlugt, Todd N. Eagar, C. Nickerson-Nutter, R. Nazareno, V. K. Kuchroo, S. D. Miller

Initial migration of encephalitogenic T cells to the central nervous system (CNS) in relapsing experimental autoimmune encephalomyelitis (R-EAE), an animal model of multiple sclerosis (MS), depends on the interaction of the α4 integrin (VLA-4) expressed on activated T cells with VCAM-1 expressed on activated cerebrovascular endothelial cells. Alternate homing mechanisms may be employed by infiltrating inflammatory cells after disease onset. We thus compared the ability of anti-VLA-4 to regulate proteolipid protein (PLP) 139-151-induced R-EAE when administered either before or after disease onset. Preclinical administration of anti-VLA-4 either to naive recipients of primed encephalitogenic T cells or to mice 1 week after peptide priming, i.e., before clinical disease onset, inhibited the onset and severity of clinical disease. In contrast, Ab treatment either at the peak of acute disease or during remission exacerbated disease relapses and increased the accumulation of CD4+ T cells in the CNS. Most significantly, anti-VLA-4 treatment either before or during ongoing R-EAE enhanced Th1 responses to both the priming peptide and endogenous myelin epitopes released secondary to acute tissue damage. Collectively, these results suggest that treatment with anti-VLA-4 Ab has multiple effects on the immune system and may be problematic in treating established autoimmune diseases such as MS.

Original languageEnglish (US)
Pages (from-to)995-1006
Number of pages12
JournalJournal of Clinical Investigation
Volume107
Issue number8
DOIs
StatePublished - Jan 1 2001

PMID: 11306603

PMCID: PMC199558

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Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis. / Theien, B. E.; Vanderlugt, C. L.; Eagar, Todd N.; Nickerson-Nutter, C.; Nazareno, R.; Kuchroo, V. K.; Miller, S. D.

In: Journal of Clinical Investigation, Vol. 107, No. 8, 01.01.2001, p. 995-1006.

Research output: Contribution to journalArticle

Harvard

Theien, BE, Vanderlugt, CL, Eagar, TN, Nickerson-Nutter, C, Nazareno, R, Kuchroo, VK & Miller, SD 2001, 'Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis' Journal of Clinical Investigation, vol. 107, no. 8, pp. 995-1006. https://doi.org/10.1172/JCI11717

APA

Theien, B. E., Vanderlugt, C. L., Eagar, T. N., Nickerson-Nutter, C., Nazareno, R., Kuchroo, V. K., & Miller, S. D. (2001). Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis. Journal of Clinical Investigation, 107(8), 995-1006. https://doi.org/10.1172/JCI11717

Vancouver

Theien BE, Vanderlugt CL, Eagar TN, Nickerson-Nutter C, Nazareno R, Kuchroo VK et al. Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis. Journal of Clinical Investigation. 2001 Jan 1;107(8):995-1006. https://doi.org/10.1172/JCI11717

Author

Theien, B. E. ; Vanderlugt, C. L. ; Eagar, Todd N. ; Nickerson-Nutter, C. ; Nazareno, R. ; Kuchroo, V. K. ; Miller, S. D. / Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis. In: Journal of Clinical Investigation. 2001 ; Vol. 107, No. 8. pp. 995-1006.

BibTeX

@article{fd5297ac4217405d97a701bdf88b68cb,
title = "Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis",
abstract = "Initial migration of encephalitogenic T cells to the central nervous system (CNS) in relapsing experimental autoimmune encephalomyelitis (R-EAE), an animal model of multiple sclerosis (MS), depends on the interaction of the α4 integrin (VLA-4) expressed on activated T cells with VCAM-1 expressed on activated cerebrovascular endothelial cells. Alternate homing mechanisms may be employed by infiltrating inflammatory cells after disease onset. We thus compared the ability of anti-VLA-4 to regulate proteolipid protein (PLP) 139-151-induced R-EAE when administered either before or after disease onset. Preclinical administration of anti-VLA-4 either to naive recipients of primed encephalitogenic T cells or to mice 1 week after peptide priming, i.e., before clinical disease onset, inhibited the onset and severity of clinical disease. In contrast, Ab treatment either at the peak of acute disease or during remission exacerbated disease relapses and increased the accumulation of CD4+ T cells in the CNS. Most significantly, anti-VLA-4 treatment either before or during ongoing R-EAE enhanced Th1 responses to both the priming peptide and endogenous myelin epitopes released secondary to acute tissue damage. Collectively, these results suggest that treatment with anti-VLA-4 Ab has multiple effects on the immune system and may be problematic in treating established autoimmune diseases such as MS.",
author = "Theien, {B. E.} and Vanderlugt, {C. L.} and Eagar, {Todd N.} and C. Nickerson-Nutter and R. Nazareno and Kuchroo, {V. K.} and Miller, {S. D.}",
year = "2001",
month = "1",
day = "1",
doi = "10.1172/JCI11717",
language = "English (US)",
volume = "107",
pages = "995--1006",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "8",

}

RIS

TY - JOUR

T1 - Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis

AU - Theien, B. E.

AU - Vanderlugt, C. L.

AU - Eagar, Todd N.

AU - Nickerson-Nutter, C.

AU - Nazareno, R.

AU - Kuchroo, V. K.

AU - Miller, S. D.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Initial migration of encephalitogenic T cells to the central nervous system (CNS) in relapsing experimental autoimmune encephalomyelitis (R-EAE), an animal model of multiple sclerosis (MS), depends on the interaction of the α4 integrin (VLA-4) expressed on activated T cells with VCAM-1 expressed on activated cerebrovascular endothelial cells. Alternate homing mechanisms may be employed by infiltrating inflammatory cells after disease onset. We thus compared the ability of anti-VLA-4 to regulate proteolipid protein (PLP) 139-151-induced R-EAE when administered either before or after disease onset. Preclinical administration of anti-VLA-4 either to naive recipients of primed encephalitogenic T cells or to mice 1 week after peptide priming, i.e., before clinical disease onset, inhibited the onset and severity of clinical disease. In contrast, Ab treatment either at the peak of acute disease or during remission exacerbated disease relapses and increased the accumulation of CD4+ T cells in the CNS. Most significantly, anti-VLA-4 treatment either before or during ongoing R-EAE enhanced Th1 responses to both the priming peptide and endogenous myelin epitopes released secondary to acute tissue damage. Collectively, these results suggest that treatment with anti-VLA-4 Ab has multiple effects on the immune system and may be problematic in treating established autoimmune diseases such as MS.

AB - Initial migration of encephalitogenic T cells to the central nervous system (CNS) in relapsing experimental autoimmune encephalomyelitis (R-EAE), an animal model of multiple sclerosis (MS), depends on the interaction of the α4 integrin (VLA-4) expressed on activated T cells with VCAM-1 expressed on activated cerebrovascular endothelial cells. Alternate homing mechanisms may be employed by infiltrating inflammatory cells after disease onset. We thus compared the ability of anti-VLA-4 to regulate proteolipid protein (PLP) 139-151-induced R-EAE when administered either before or after disease onset. Preclinical administration of anti-VLA-4 either to naive recipients of primed encephalitogenic T cells or to mice 1 week after peptide priming, i.e., before clinical disease onset, inhibited the onset and severity of clinical disease. In contrast, Ab treatment either at the peak of acute disease or during remission exacerbated disease relapses and increased the accumulation of CD4+ T cells in the CNS. Most significantly, anti-VLA-4 treatment either before or during ongoing R-EAE enhanced Th1 responses to both the priming peptide and endogenous myelin epitopes released secondary to acute tissue damage. Collectively, these results suggest that treatment with anti-VLA-4 Ab has multiple effects on the immune system and may be problematic in treating established autoimmune diseases such as MS.

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U2 - 10.1172/JCI11717

DO - 10.1172/JCI11717

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JF - Journal of Clinical Investigation

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IS - 8

ER -

ID: 16833165