Tc1/Tc2 and Th1/Th2 balance in Asian and Western types of multiple sclerosis, HTLV-I-associated myelopathy/tropical spastic paraparesis and hyperIgEaemic myelitis

Hirofumi Ochi, Xiao Mu Wu, Manabu Osoegawa, Izumi Horiuchi, Motozumi Minohara, Hiroyuki Murai, Yasumasa Ohyagi, Hirokazu Furuya, Jun ichi Kira

Research output: Contribution to journalArticle

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Abstract

CD8+ T cells, like CD4+ T cells, can differentiate into at least two subsets with distinct cytokine patterns: Tc1 cells produce Th1-like cytokines and Tc2 cells produce Th2-like cytokines. To clarify the immunopathological roles of Tc1 and Tc2 cells in central nervous system (CNS) inflammation, we examined intracellular cytokines in CD8+ and CD4+ T cells by flow cytometry and analyzed the Tc1/Tc2 balance as well as the Th1/Th2 balance in 80 patients with various CNS inflammatory diseases, including 20 with optico-spinal multiple sclerosis (OS-MS), 21 with conventional MS (C-MS), 22 with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 17 with hyperIgEaemic myelitis. Twenty-two healthy subjects were also examined as controls. Patients with OS-MS showed a significantly higher percentage of INF-γ+IL-4- CD8+ T cells as well as CD4+ T cells and a significantly higher intracellular interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio both in CD8+ and CD4+ T cells throughout the relapse and remission phases than the healthy controls. Furthermore, the patients with OS-MS showed a significantly lower percentage of INF-γ-IL-4+ CD4+ T cells as well as CD8+ T cells during the relapse phase than the healthy controls. On the other hand, the patients with C-MS showed a significantly higher percentage of IFN-γ-IL-4+ CD8+ T cells in addition to more IFN-γ+IL-4- CD4+ T cells during the relapse phase than the healthy controls. The HAM/TSP patients showed a significantly higher percentage of INF-γ+IL-4- CD8+ T cells and a significantly higher intracellular IFN-γ/IL-4 ratio in CD8+ T cells than the healthy controls. In contrast, in hyperIgEaemic myelitis, in addition to a significantly lower intracellular IFN-γ/IL-4 ratio in CD4+ T cells, a tendency toward a lower intracellular IFN-γ/IL-4 ratio in CD8+ T cells in comparison to the healthy controls was observed. These results clarified for the first time the distinct Tc1/Tc2 balance in each disease condition as follows: Tc1 cell response is predominant in OS-MS and HAM/TSP, while Tc2 cell response is predominant in hyperIgEaemic myelitis and at relapse phase of C-MS. Furthermore, our results suggest that CD8+ T cells play an adjunctive role in disease induction and the clinical course of MS.

Original languageEnglish
Pages (from-to)297-305
Number of pages9
JournalJournal of Neuroimmunology
Volume119
Issue number2
DOIs
Publication statusPublished - Oct 1 2001

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Th1-Th2 Balance
Tropical Spastic Paraparesis
Myelitis
Spinal Cord Diseases
Multiple Sclerosis
Viruses
T-Lymphocytes
Interleukin-4
Interferons
Cytokines
Recurrence
Th2 Cells
Th1 Cells
Central Nervous System Diseases

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Cite this

Tc1/Tc2 and Th1/Th2 balance in Asian and Western types of multiple sclerosis, HTLV-I-associated myelopathy/tropical spastic paraparesis and hyperIgEaemic myelitis. / Ochi, Hirofumi; Wu, Xiao Mu; Osoegawa, Manabu; Horiuchi, Izumi; Minohara, Motozumi; Murai, Hiroyuki; Ohyagi, Yasumasa; Furuya, Hirokazu; Kira, Jun ichi.

In: Journal of Neuroimmunology, Vol. 119, No. 2, 01.10.2001, p. 297-305.

Research output: Contribution to journalArticle

Ochi, Hirofumi ; Wu, Xiao Mu ; Osoegawa, Manabu ; Horiuchi, Izumi ; Minohara, Motozumi ; Murai, Hiroyuki ; Ohyagi, Yasumasa ; Furuya, Hirokazu ; Kira, Jun ichi. / Tc1/Tc2 and Th1/Th2 balance in Asian and Western types of multiple sclerosis, HTLV-I-associated myelopathy/tropical spastic paraparesis and hyperIgEaemic myelitis. In: Journal of Neuroimmunology. 2001 ; Vol. 119, No. 2. pp. 297-305.
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T1 - Tc1/Tc2 and Th1/Th2 balance in Asian and Western types of multiple sclerosis, HTLV-I-associated myelopathy/tropical spastic paraparesis and hyperIgEaemic myelitis

AU - Ochi, Hirofumi

AU - Wu, Xiao Mu

AU - Osoegawa, Manabu

AU - Horiuchi, Izumi

AU - Minohara, Motozumi

AU - Murai, Hiroyuki

AU - Ohyagi, Yasumasa

AU - Furuya, Hirokazu

AU - Kira, Jun ichi

PY - 2001/10/1

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N2 - CD8+ T cells, like CD4+ T cells, can differentiate into at least two subsets with distinct cytokine patterns: Tc1 cells produce Th1-like cytokines and Tc2 cells produce Th2-like cytokines. To clarify the immunopathological roles of Tc1 and Tc2 cells in central nervous system (CNS) inflammation, we examined intracellular cytokines in CD8+ and CD4+ T cells by flow cytometry and analyzed the Tc1/Tc2 balance as well as the Th1/Th2 balance in 80 patients with various CNS inflammatory diseases, including 20 with optico-spinal multiple sclerosis (OS-MS), 21 with conventional MS (C-MS), 22 with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 17 with hyperIgEaemic myelitis. Twenty-two healthy subjects were also examined as controls. Patients with OS-MS showed a significantly higher percentage of INF-γ+IL-4- CD8+ T cells as well as CD4+ T cells and a significantly higher intracellular interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio both in CD8+ and CD4+ T cells throughout the relapse and remission phases than the healthy controls. Furthermore, the patients with OS-MS showed a significantly lower percentage of INF-γ-IL-4+ CD4+ T cells as well as CD8+ T cells during the relapse phase than the healthy controls. On the other hand, the patients with C-MS showed a significantly higher percentage of IFN-γ-IL-4+ CD8+ T cells in addition to more IFN-γ+IL-4- CD4+ T cells during the relapse phase than the healthy controls. The HAM/TSP patients showed a significantly higher percentage of INF-γ+IL-4- CD8+ T cells and a significantly higher intracellular IFN-γ/IL-4 ratio in CD8+ T cells than the healthy controls. In contrast, in hyperIgEaemic myelitis, in addition to a significantly lower intracellular IFN-γ/IL-4 ratio in CD4+ T cells, a tendency toward a lower intracellular IFN-γ/IL-4 ratio in CD8+ T cells in comparison to the healthy controls was observed. These results clarified for the first time the distinct Tc1/Tc2 balance in each disease condition as follows: Tc1 cell response is predominant in OS-MS and HAM/TSP, while Tc2 cell response is predominant in hyperIgEaemic myelitis and at relapse phase of C-MS. Furthermore, our results suggest that CD8+ T cells play an adjunctive role in disease induction and the clinical course of MS.

AB - CD8+ T cells, like CD4+ T cells, can differentiate into at least two subsets with distinct cytokine patterns: Tc1 cells produce Th1-like cytokines and Tc2 cells produce Th2-like cytokines. To clarify the immunopathological roles of Tc1 and Tc2 cells in central nervous system (CNS) inflammation, we examined intracellular cytokines in CD8+ and CD4+ T cells by flow cytometry and analyzed the Tc1/Tc2 balance as well as the Th1/Th2 balance in 80 patients with various CNS inflammatory diseases, including 20 with optico-spinal multiple sclerosis (OS-MS), 21 with conventional MS (C-MS), 22 with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 17 with hyperIgEaemic myelitis. Twenty-two healthy subjects were also examined as controls. Patients with OS-MS showed a significantly higher percentage of INF-γ+IL-4- CD8+ T cells as well as CD4+ T cells and a significantly higher intracellular interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio both in CD8+ and CD4+ T cells throughout the relapse and remission phases than the healthy controls. Furthermore, the patients with OS-MS showed a significantly lower percentage of INF-γ-IL-4+ CD4+ T cells as well as CD8+ T cells during the relapse phase than the healthy controls. On the other hand, the patients with C-MS showed a significantly higher percentage of IFN-γ-IL-4+ CD8+ T cells in addition to more IFN-γ+IL-4- CD4+ T cells during the relapse phase than the healthy controls. The HAM/TSP patients showed a significantly higher percentage of INF-γ+IL-4- CD8+ T cells and a significantly higher intracellular IFN-γ/IL-4 ratio in CD8+ T cells than the healthy controls. In contrast, in hyperIgEaemic myelitis, in addition to a significantly lower intracellular IFN-γ/IL-4 ratio in CD4+ T cells, a tendency toward a lower intracellular IFN-γ/IL-4 ratio in CD8+ T cells in comparison to the healthy controls was observed. These results clarified for the first time the distinct Tc1/Tc2 balance in each disease condition as follows: Tc1 cell response is predominant in OS-MS and HAM/TSP, while Tc2 cell response is predominant in hyperIgEaemic myelitis and at relapse phase of C-MS. Furthermore, our results suggest that CD8+ T cells play an adjunctive role in disease induction and the clinical course of MS.

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