Adjuvant Arthritis

Wauben, Marca H. M.; Wagenaar-Hilbers, Josée P A; Eden, Willem van

doi:10.1016/b978-0-08-091736-8.50017-9

Cited by 11 publications

(17 citation statements)

References 62 publications

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“…Indeed, AA itself is known to induce regulatory cells. Rats recovered from AA acquire resistance to further attempts to induce the disease (1).…”

Section: Discussionmentioning

confidence: 99%

“…AA is induced in Lewis rats by immunization with heat-killed Mycobacterium tuberculosis (Mt) suspended in IFA (1). T cell reactivity against the mycobacterial 65-kDa heat shock protein (HSP65) is involved in the progression of AA.…”

mentioning

confidence: 99%

“…A djuvant arthritis (AA) 3 is an experimental autoimmune disease that models several features of human rheumatoid arthritis (1). AA is induced in Lewis rats by immunization with heat-killed Mycobacterium tuberculosis (Mt) suspended in IFA (1).…”

mentioning

confidence: 99%

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DNA Fragments of the Human 60-kDa Heat Shock Protein (HSP60) Vaccinate Against Adjuvant Arthritis: Identification of a Regulatory HSP60 Peptide

Quintana

Carmi

Mor

et al. 2003

The Journal of Immunology

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Adjuvant arthritis (AA) is induced by immunizing Lewis rats with Mycobacterium tuberculosis suspended in adjuvant. The mycobacterial 65-kDa heat shock protein (HSP65) contains at least one epitope associated with the pathogenesis of AA: T cell clones that recognize an epitope formed by aa 180–188 of HSP65 react with self-cartilage and can adoptively transfer AA. Nevertheless, vaccination with HSP65 or some of its T cell epitopes can prevent AA by a mechanism that seems to involve cross-reactivity with the self-60-kDa HSP60. We recently demonstrated that DNA vaccination with the human hsp60 gene can inhibit AA. In the present work, we searched for regulatory epitopes using DNA vaccination with HSP60 gene fragments. We now report that specific HSP60 DNA fragments can serve as effective vaccines. Using overlapping HSP60 peptides, we identified a regulatory peptide (Hu3) that was specifically recognized by the T cells of DNA-vaccinated rats. Vaccination with Hu3, or transfer of splenocytes from Hu3-vaccinated rats, inhibited the development of AA. Vaccination with the mycobacterial homologue of Hu3 had no effect. Effective DNA or peptide vaccination was associated with enhanced T cell proliferation to a variety of disease-associated Ags, along with a Th2/3-like shift (down-regulation of IFN-γ secretion and enhanced secretion of IL-10 and/or tumor growth factor β1) in response to peptide Mt176–190 (the 180–188 epitope of HSP65). The regulatory response to HSP60 or its Hu3 epitope included both Th1 (IFN-γ) and Th2/3 (IL-10/tumor growth factor β1) secretors. These results show that regulatory mechanisms can be activated by immunization with relevant self-HSP60 epitopes.

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“…Indeed, AA itself is known to induce regulatory cells. Rats recovered from AA acquire resistance to further attempts to induce the disease (1).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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DNA Fragments of the Human 60-kDa Heat Shock Protein (HSP60) Vaccinate Against Adjuvant Arthritis: Identification of a Regulatory HSP60 Peptide

Quintana

Carmi

Mor

et al. 2003

The Journal of Immunology

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“…A djuvant arthritis (AA), 3 inducible in susceptible rats by immunization with heat-killed Mycobacterium tuberculosis (Mt), is characterized by peripheral joint lesions that share many features with human rheumatoid arthritis (RA), although certainly not all features (1). Mycobacterial 65-kDa heat shock protein (HSP65) is a target of pathogenic T cells in AA; a T cell clone (A2b) specific for the epitope contained between amino acids 180 and 188 of HSP65 could adoptively transfer AA (2).…”

Section: Inhibition Of Adjuvant Arthritis By a Dna Vaccine Encodingmentioning

confidence: 99%

“…Human Heat Shock Protein 60 1 Francisco J. Quintana, Pnina Carmi, Felix Mor, and Irun R. Cohen 2 Adjuvant arthritis (AA) is an autoimmune disease inducible in rats involving T cell reactivity to the mycobacterial 65-kDa heat shock protein (HSP65). HSP65-specific T cells cross-reactive with the mammalian 60-kDa heat shock protein (HSP60) are thought to participate in the modulation of AA.…”

Section: Inhibition Of Adjuvant Arthritis By a Dna Vaccine Encodingmentioning

confidence: 99%

Inhibition of Adjuvant Arthritis by a DNA Vaccine Encoding Human Heat Shock Protein 60

Quintana

Carmi

Mor

et al. 2002

The Journal of Immunology

128

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Adjuvant arthritis (AA) is an autoimmune disease inducible in rats involving T cell reactivity to the mycobacterial 65-kDa heat shock protein (HSP65). HSP65-specific T cells cross-reactive with the mammalian 60-kDa heat shock protein (HSP60) are thought to participate in the modulation of AA. In this work we studied the effects on AA of DNA vaccination using constructs coding for HSP65 (pHSP65) or human HSP60 (pHSP60). We found that both constructs could inhibit AA, but that pHSP60 was more effective than pHSP65. The immune effects associated with specific DNA-induced suppression of AA were complex and included enhanced T cell proliferation to a variety of disease-associated Ags. Effective vaccination with HSP60 or HSP65 DNA led paradoxically to up-regulation of IFN-γ secretion to HSP60 and, concomitantly, to down-regulation of IFN-γ secretion to the P180-188 epitope of HSP65. There were also variable changes in the profiles of IL-10 secretion to different Ags. However, vaccination with pHSP60 or pHSP65 enhanced the production of TGFβ1 to both HSP60 and HSP65 epitopes. Our results support a regulatory role for HSP60 autoreactivity in AA and demonstrate that this control mechanism can be activated by DNA vaccination with both HSP60 or HSP65.

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Inhibition of adjuvant‐induced arthritis by DNA vaccination with the 70‐kd or the 90‐kd human heat‐shock protein: Immune cross‐regulation with the 60‐kd heat‐shock protein

Quintana¹,

Carmi²,

Mor³

et al. 2004

Arthritis & Rheumatism

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Adjuvant Arthritis

Cited by 11 publications

References 62 publications

DNA Fragments of the Human 60-kDa Heat Shock Protein (HSP60) Vaccinate Against Adjuvant Arthritis: Identification of a Regulatory HSP60 Peptide

DNA Fragments of the Human 60-kDa Heat Shock Protein (HSP60) Vaccinate Against Adjuvant Arthritis: Identification of a Regulatory HSP60 Peptide

Inhibition of Adjuvant Arthritis by a DNA Vaccine Encoding Human Heat Shock Protein 60

Inhibition of adjuvant‐induced arthritis by DNA vaccination with the 70‐kd or the 90‐kd human heat‐shock protein: Immune cross‐regulation with the 60‐kd heat‐shock protein

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