Myelin Basic Protein–specific T Helper 2 (Th2) Cells Cause Experimental Autoimmune Encephalomyelitis in Immunodeficient Hosts Rather than Protect Them from the Disease

Abstract

Chronic inflammatory autoimmune diseases such as multiple sclerosis, diabetes, and rheumatoid arthritis are caused by CD4+ Th1 cells. Because Th2 cells antagonize Th1 cell functions in several ways, it is believed that immune deviation towards Th2 can prevent or cure autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease used as a model for multiple sclerosis. Using an adoptive transfer system we assessed the role of Th1 and Th2 cells in EAE. In vitro generated Th1 and Th2 cells from myelin basic protein (MBP)-specific TCR transgenic mice were transferred into normal and immunodeficient mice. Th1 cells caused EAE in all recipients after a brief preclinical phase. Surprisingly, Th2 cells also caused EAE in RAG-1 KO mice and in αβ T cell–deficient mice, albeit after a longer preclinical phase. Normal or γδ T cell–deficient mice were resistant to EAE induced by Th2 cells. The histopathological features of this disease resembled those of an allergic process. In addition, disease induction by Th1 cells was not altered by coadmininstration of Th2 cells in any of the recipients. These findings indicate that MBP-specific Th2 cells have the potential to induce EAE and that the disease induced by previously activated Th1 cells cannot be prevented by normal lymphocytes nor by previously activated Th2 cells.

Revisiting Tolerance Induced by Autoantigen in Incomplete Freund’s Adjuvant

“…Histologic sections of CNS or kidney tissue from Ag: IFA-injected animals were indistinguishable from those of naive mice, even up to 24 wk after the initial injection. We specifically did not see any evidence of eosinophilic infiltration that might be associated with type 2 immune responses (33)(34)(35). In our hands, therefore, the classic CFA/IFA paradigm holds with respect to disease induction for three models of EAE and for ␣TBM disease: immunization in CFA induces autoimmune disease, and injection in IFA does not.…”

“…This view has more recently come under significant scrutiny. It was shown, for example, that the cotransfer of autoreactive, Th2-polarized, putative regulatory T cells with Th1-polarized effector T cells did not prevent or ameliorate autoimmune pathology, even when the Th2 cells were in marked excess over the Th1 cells (33)(34)(35). To the contrary, such adoptive transfers indicated that the autoreactive Th2 cells could themselves induce inflammatory responses in the target organ, thus contributing to tissue destruction.…”

IL-23 Is Critical in the Induction but Not in the Effector Phase of Experimental Autoimmune Encephalomyelitis

“…Many studies have implicated Th1 cells in pathogenesis of EAE (3)(4)(5)(6)(7). In a recent report, IL-17-producing Th17 cells have been suggested to be an important encephalitogenic T cell subset (8).…”

“…EAE shares many clinical and histopathological features with multiple sclerosis (MS) and is a commonly used animal model of this human autoimmune disease (1,2). EAE is believed to be a Th1-induced autoimmune disease because of the increased expression of Th1 cytokines in the affected CNS and because injection of myelin specific CD4 ϩ Th1 but not Th2 cells into immunocompetent mice is sufficient to induce EAE (3)(4)(5)(6)(7). More recently, IL-17-producing Th17 cells have been implicated in pathogenesis of EAE (8 -10).…”

Extracellular lysosome‐associated membrane protein‐1 (LAMP‐1) mediates autoimmune disease progression in the NOD model of type 1 diabetes

“…B10.PL wild-type (WT) mice were purchased from The Jackson Laboratory (Bar Harbor, ME). MBP-TCR transgenic mice [34] were a generous gift from Dr. J. Lafaille, and were reared in our animal facilities under specific pathogen-free conditions. NOD and B10.PL WT animals were housed in a conventional mouse facility.…”