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The activation status of neuroantigen-specific T cells in the target organ determines the clinical outcome of autoimmune encephalomyelitis.

Kawakami N, Lassmann S, Li Z, Odoardi F, Ritter T, Ziemssen T, Klinkert WE, Ellwart JW, Bradl M, Krivacic K, Lassmann H, Ransohoff RM, Volk HD, Wekerle H, Linington C, Flügel A - J. Exp. Med. (2004)

Bottom Line: Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue.However, exclusively highly pathogenic T cells were significantly reactivated within the CNS.Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroimmunology, Max-Planck Institute for Neurobiology, 82152 Martinsried, Germany.

ABSTRACT
The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)-specific T cells in Lewis rats, whereas transfer of S100beta- or myelin oligodendrocyte glycoprotein (MOG)-specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein(+) T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo.

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Relative numbers of TGFP cells infiltrating the CNS in the course of tEAE. The number of CNS-infiltrating GFP-positive T cells in the CD4+ cell population was analyzed 4 d after transfer. TMBP-GFP (A), TDA-MOG-GFP (B), TS100β-GFP (C), and TLE-MOG-GFP (D) cells are shown. The majority of CD4+ T cells were GFP positive in all cell lines tested. Representative data of at least three independent experiments/TCLs are shown.
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fig1: Relative numbers of TGFP cells infiltrating the CNS in the course of tEAE. The number of CNS-infiltrating GFP-positive T cells in the CD4+ cell population was analyzed 4 d after transfer. TMBP-GFP (A), TDA-MOG-GFP (B), TS100β-GFP (C), and TLE-MOG-GFP (D) cells are shown. The majority of CD4+ T cells were GFP positive in all cell lines tested. Representative data of at least three independent experiments/TCLs are shown.

Mentions: FACS® analysis further revealed that large numbers of these GFP-labeled T cells invaded the CNS irrespective of their autoantigen specificity (Fig. 1) . 4 d after the transfer of TMBP-GFP, TS100β-GFP, TLE-MOG-GFP, or TDA-MOG-GFP effector T cells, the majority (75–94%) of CD4+ T cells infiltrating the CNS expressed GFP (Fig. 1). In all cases, this very high proportion of GFP-expressing effector T cells initially present in the infiltrates decreased to <10% within the following 72 h (unpublished data).


The activation status of neuroantigen-specific T cells in the target organ determines the clinical outcome of autoimmune encephalomyelitis.

Kawakami N, Lassmann S, Li Z, Odoardi F, Ritter T, Ziemssen T, Klinkert WE, Ellwart JW, Bradl M, Krivacic K, Lassmann H, Ransohoff RM, Volk HD, Wekerle H, Linington C, Flügel A - J. Exp. Med. (2004)

Relative numbers of TGFP cells infiltrating the CNS in the course of tEAE. The number of CNS-infiltrating GFP-positive T cells in the CD4+ cell population was analyzed 4 d after transfer. TMBP-GFP (A), TDA-MOG-GFP (B), TS100β-GFP (C), and TLE-MOG-GFP (D) cells are shown. The majority of CD4+ T cells were GFP positive in all cell lines tested. Representative data of at least three independent experiments/TCLs are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211765&req=5

fig1: Relative numbers of TGFP cells infiltrating the CNS in the course of tEAE. The number of CNS-infiltrating GFP-positive T cells in the CD4+ cell population was analyzed 4 d after transfer. TMBP-GFP (A), TDA-MOG-GFP (B), TS100β-GFP (C), and TLE-MOG-GFP (D) cells are shown. The majority of CD4+ T cells were GFP positive in all cell lines tested. Representative data of at least three independent experiments/TCLs are shown.
Mentions: FACS® analysis further revealed that large numbers of these GFP-labeled T cells invaded the CNS irrespective of their autoantigen specificity (Fig. 1) . 4 d after the transfer of TMBP-GFP, TS100β-GFP, TLE-MOG-GFP, or TDA-MOG-GFP effector T cells, the majority (75–94%) of CD4+ T cells infiltrating the CNS expressed GFP (Fig. 1). In all cases, this very high proportion of GFP-expressing effector T cells initially present in the infiltrates decreased to <10% within the following 72 h (unpublished data).

Bottom Line: Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue.However, exclusively highly pathogenic T cells were significantly reactivated within the CNS.Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroimmunology, Max-Planck Institute for Neurobiology, 82152 Martinsried, Germany.

ABSTRACT
The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)-specific T cells in Lewis rats, whereas transfer of S100beta- or myelin oligodendrocyte glycoprotein (MOG)-specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein(+) T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo.

Show MeSH
Related in: MedlinePlus