Intranasal Administration of Retinal Antigens Induces Transient T cell Activation and Apoptosis within Drainage Lymph Nodes but not Spleen

doi:10.1006/jaut.1998.0269

Journal of Autoimmunity

Volume 12, Issue 3, May 1999, Pages 145-155

https://doi.org/10.1006/jaut.1998.0269 Get rights and content

Abstract

Mechanisms of mucosal tolerance induction, including anergy/deletion and active suppression are frequently described as mutually exclusive; dependent upon nature, dose and route of antigen administration. We have previously described induction of low-dose tolerance with administration of retinal autoantigens via the nasorespiratory tract which is antigen-specific, suppresses both cell mediated immunity and ultimately tissue destruction in experimental autoimmune uveoretinitis (EAU) and is mediated by splenic-derived regulatory cells. The present data further shows that splenocytes or fractionated splenic T cells, which secrete IL-4 and IL-10 when stimulated with retinal antigen in vitro , and not regional drainage lymph node cells transfer tolerance to naı̈ve animals. Analysis of apparent mechanistic differences shows that during intranasal antigen administration, the proportion of CD4⁺T cells within drainage lymph nodes increases, concurrent with a burst of IFN-γ Following subsequent antigen challenge, T cells downregulate αβTCR expression and undergo apoptosis in regional drainage lymph nodes. An increase in functional Th2 cytokine activity was noted in both Con-A and retinal antigen stimulated lymph node cultures in tolerised animals. T cells from tolerized animals secreted IL-4, whereas IL-10 was secreted predominantly by the non-T cell population present equally in control and tolerized animals. Therefore, spleen derived regulatory cells which suppress Th1 responses and T cell deletion/apoptosis in regional drainage lymph nodes are mechanisms which co-exist in tolerant rats. Th2 cytokine production after immunization appears consequential to tolerance-induced Th1 suppression.

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The role of T cell non-responsiveness following delivery of antigen via nasal mucosa is well established, as is the ability of this technique to suppress experimental autoimmunity such as experimental autoimmune uveoretinitis (EAU); [4,21–25] and experimental autoimmune encephalomyelitis (EAE) [26–32].
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^f1: Correspondence to: Dr Andrew D. Dick, Department of Ophthalmology, University of Aberdeen Medical School, Foresterhill, Aberdeen AB25 2ZD, UK. Fax: 44–1224 685158. E-mail:[email protected]

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Regular ArticleIntranasal Administration of Retinal Antigens Induces Transient T cell Activation and Apoptosis within Drainage Lymph Nodes but not Spleen

Abstract

Am. J. Ophthalmol.

J. Neuroimmunol.

J. Autoimmunity

J. Immun. Meth.

Cell. Immunol.

Down-regulation of immune responses to inhaled antigen: studies on the mechanism of induced suppression

Immunology

Nasal tolerance in experimental autoimmune myasthenia gravis (EAMG): induction of protective tolerance in primed animals

Clin. Exp. Immunol.

Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes

J. Exp. Med.

Suppression of murine collagen-induced arthritis by nasal administration of collagen

Immunology

Inhibition of experimental autoimmune encephalomyelitis by inhalation but not oral administration of the encephalitogenic peptide: influence of MHC binding affinity

Int. Immunol.

Nasal administration of retinal antigens suppresses the inflammatory response in experimental allergic uveoretinitis

Brit. J. Ophthalmol

Mucosa specific lymphocytes in the human conjunctiva, corneoscleral limbus and lacrimal gland

Curr. Eye Res.

Intranasal administration of retinal antigens suppresses retinal antigen-induced experimental autoimmune uveoretinitis

Immunology

Inhibition of experimental autoimmune uveoretinitis by oral administration of S-Ag and synthetic peptides

Autoimmunity

Inhibition of S-Ag induced experimental autoimmune uveoretinitis by oral induction of tolerance with S-Ag

J. Immunol.

Oral tolerance in myelin basic protein T cell receptor transgenic mice: suppression of autoimmune encephalomyelitis and dose-dependent induction of regulatory cells

Proc. Natl. Acad. Sci. USA

Complexities of applying nasal tolerance induction as a therapy for ongoing relapsing experimental autoimmune encephalomyelitis (EAE) in DA rats

Clin. Exp. Immunol.

Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis

J. Exp. Med.

Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis (EAU): induction of protective tolerance in primed animals

Clin. Exp. Immunol.

Suppression of EAE by oral administration of myelin basic protein: suppression of the disease in in vitro immune responses is mediated by antigen-specific CD8+cells

J. Immunol.

Aerosol insulin induces regulatory CD8 γδ T cells that prevent murine insulin-dependent diabetes

J. Exp. Med.

Regulation of IgE responses to inhaled antigens in mice by antigen-specific γδ T cells

Science

Orally induced, peptide-specific γδ TCR+cells suppress experimental autoimmune uveitis

Eur. J. Immunol.

Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-β1-secreting Th3 cells by oral administration of myelin in multiple sclerosis patients

J. Clin. Invest.

Direct evidence for anergy in T lymphocytes tolerised by oral administration of ovalbumin

Eur. J. Immunol.

In vivo tolerisation of Th1 lymphocytes following a single feeding with ovalbumin: anergy in the absence of suppression

Eur. J. Immunol.

Orally induced bystander suppression in experimental autoimmune uveiretinitis occurs only in the periphery and not in the eye

Eur. J. Immunol.

Regular Article
Intranasal Administration of Retinal Antigens Induces Transient T cell Activation and Apoptosis within Drainage Lymph Nodes but not Spleen

Suppression of EAE by oral administration of myelin basic protein: suppression of the disease in in vitro immune responses is mediated by antigen-specific CD8⁺cells

Orally induced, peptide-specific γδ TCR⁺cells suppress experimental autoimmune uveitis