The Th2 cytokine IL-4 is not required for the progression of antibody- dependent autoimmune myasthenia gravis

Balaji Balasa, Caishu Deng, Jae Lee, Premkumar Christadoss, Nora E Sarvetnick

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Experimental autoimmune myasthenia gravis (EAMG), a disorder of the neuromuscular junction, is mediated by autoantibodies against muscle nicotinic acetylcholine receptor (AChR). The roles of IFN-γ (Th1) and IL-4 (Th2) cytokines in the initiation and progression of this disease are not fully understood. Recently, we have demonstrated that IFN-γ is necessary for the initiation of tAChR-induced EAMG in mice. However, the role of IL-4 in the progression of clinical EAMG remained undetermined. In this study we have addressed the contribution of IL-4 in the disease progression in IL-4(-/-) C57BL/6j mice whose IL-4 gene has been disrupted. Following immunization with Torpedo (t) AChR, the IL-4(-/-) mice readily developed signs of muscle weakness and succumbed to clinical EAMG with kinetics similar to the susceptibility of IL-4(+/+) mice. The tAChR-primed lymph node cells from IL- 4(-/-) mice vigorously proliferated to tAChR and to its dominant α146- 162 sequence associated with disease pathogenesis. However, these T cells secreted higher levels of IFN-γ and IL-2, suggesting the development of a Th1 default pathway in these mice. Nevertheless, the IL-4 mutation had no effect on the recruitment of CD4+Vβ6+ T cells specific to the dominant tAChR α146-162 sequence in vivo. Immune sera from IL-4(-/-) mice showed a dramatic increase in mouse AChR-specific IgG2a levels followed by a concomitant decrease in IgG1 levels, but these mice did not exhibit an accelerated disease. In conclusion, we have demonstrated for the first time that IL-4 is not required either for the generation of a pathogenic anti- AChR humoral immune response or for progression of clinical EAMG in mice.

Original languageEnglish (US)
Pages (from-to)2856-2862
Number of pages7
JournalJournal of Immunology
Volume161
Issue number6
StatePublished - Sep 15 1998

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Myasthenia Gravis
Interleukin-4
Autoimmune Experimental Myasthenia Gravis
Cytokines
Antibodies
Cholinergic Receptors
Disease Progression
Neuromuscular Junction Diseases
T-Lymphocytes
Torpedo
Muscle Weakness
Nicotinic Receptors
Humoral Immunity
Inbred C57BL Mouse
Autoantibodies
Interleukin-2
Immune Sera
Immunization
Immunoglobulin G
Lymph Nodes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The Th2 cytokine IL-4 is not required for the progression of antibody- dependent autoimmune myasthenia gravis. / Balasa, Balaji; Deng, Caishu; Lee, Jae; Christadoss, Premkumar; Sarvetnick, Nora E.

In: Journal of Immunology, Vol. 161, No. 6, 15.09.1998, p. 2856-2862.

Research output: Contribution to journalArticle

Balasa, Balaji ; Deng, Caishu ; Lee, Jae ; Christadoss, Premkumar ; Sarvetnick, Nora E. / The Th2 cytokine IL-4 is not required for the progression of antibody- dependent autoimmune myasthenia gravis. In: Journal of Immunology. 1998 ; Vol. 161, No. 6. pp. 2856-2862.
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abstract = "Experimental autoimmune myasthenia gravis (EAMG), a disorder of the neuromuscular junction, is mediated by autoantibodies against muscle nicotinic acetylcholine receptor (AChR). The roles of IFN-γ (Th1) and IL-4 (Th2) cytokines in the initiation and progression of this disease are not fully understood. Recently, we have demonstrated that IFN-γ is necessary for the initiation of tAChR-induced EAMG in mice. However, the role of IL-4 in the progression of clinical EAMG remained undetermined. In this study we have addressed the contribution of IL-4 in the disease progression in IL-4(-/-) C57BL/6j mice whose IL-4 gene has been disrupted. Following immunization with Torpedo (t) AChR, the IL-4(-/-) mice readily developed signs of muscle weakness and succumbed to clinical EAMG with kinetics similar to the susceptibility of IL-4(+/+) mice. The tAChR-primed lymph node cells from IL- 4(-/-) mice vigorously proliferated to tAChR and to its dominant α146- 162 sequence associated with disease pathogenesis. However, these T cells secreted higher levels of IFN-γ and IL-2, suggesting the development of a Th1 default pathway in these mice. Nevertheless, the IL-4 mutation had no effect on the recruitment of CD4+Vβ6+ T cells specific to the dominant tAChR α146-162 sequence in vivo. Immune sera from IL-4(-/-) mice showed a dramatic increase in mouse AChR-specific IgG2a levels followed by a concomitant decrease in IgG1 levels, but these mice did not exhibit an accelerated disease. In conclusion, we have demonstrated for the first time that IL-4 is not required either for the generation of a pathogenic anti- AChR humoral immune response or for progression of clinical EAMG in mice.",
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