Tolerization with Hsp65 Induces Protection Against Adjuvant-induced Arthritis by Modulating the Antigen-directed Interferon-gamma, Interleukin-17, and Antibody Responses

Overview

Journal Arthritis Rheum

Specialty Rheumatology

Date 2009 Jan 1

PMID 19116924

Citations 13

Authors

Shailesh R Satpute

Rajesh Rajaiah

Swamy K Polumuri

Kamal D Moudgil

Affiliations

Soon will be listed here.

Abstract

Objective: Pretreatment of Lewis rats with soluble mycobacterial Hsp65 affords protection against subsequent adjuvant-induced arthritis (AIA). This study was aimed at unraveling the mechanisms underlying mycobacterial Hsp65-induced protection against arthritis, using contemporary parameters of immunity.

Methods: Lewis rats were given 3 intraperitoneal injections of mycobacterial Hsp65 in solution prior to the initiation of AIA with heat-killed Mycobacterium tuberculosis. Thereafter, mycobacterial Hsp65-specific T cell proliferative, cytokine, and antibody responses were tested in tolerized rats. The roles of anergy and the indoleamine 2,3 dioxygenase (IDO)-tryptophan pathway in tolerance induction were assessed, and the frequency and suppressive function of CD4+FoxP3+ Treg cells were monitored. Also tested was the effect of mycobacterial Hsp65 tolerization on T cell responses to AIA-related mycobacterial Hsp70, mycobacterial Hsp10, and rat Hsp65.

Results: The AIA-protective effect of mycobacterial Hsp65-induced tolerance was associated with a significantly reduced T cell proliferative response to mycobacterial Hsp65, which was reversed by interleukin-2 (IL-2), indicating anergy induction. The production of interferon-gamma (but not IL-4/IL-10) was increased, with concurrent down-regulation of IL-17 expression by mycobacterial Hsp65-primed T cells. Neither the frequency nor the suppressive activity of CD4+FoxP3+ T cells changed following tolerization, but the serum level of anti-mycobacterial Hsp65 antibodies was increased. However, no evidence was observed for a role of IDO or cross-tolerance to mycobacterial Hsp70, mycobacterial Hsp10, or rat Hsp65.

Conclusion: Tolerization with soluble mycobacterial Hsp65 leads to suppression of IL-17, anergy induction, and enhanced production of anti-mycobacterial Hsp65 antibodies, which play a role in protection against AIA. These results are relevant to the development of effective immunotherapeutic approaches for autoimmune arthritis.

Citing Articles

Hsp65-Producing Prevents Antigen-Induced Arthritis in Mice.

Gusmao-Silva G, Aguiar S, Camila Goncalves Miranda M, Guimaraes M, Alves J, Vieira A Front Immunol. 2020; 11:562905.

PMID: 33072101 PMC: 7538670. DOI: 10.3389/fimmu.2020.562905.

Heat Shock Protein 70 as a Double Agent Acting Inside and Outside the Cell: Insights into Autoimmunity.

Tukaj S Int J Mol Sci. 2020; 21(15).

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Immunomodulation of autoimmune arthritis by pro-inflammatory cytokines.

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pVAXhsp65 Vaccination Primes for High IL-10 Production and Decreases Experimental Encephalomyelitis Severity.

Zorzella-Pezavento S, Chiuso-Minicucci F, Franca T, Watanabe Ishikawa L, da Rosa L, Colavite P J Immunol Res. 2017; 2017:6257958.

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Systemic Administration of Proteoglycan Protects BALB/c Retired Breeder Mice from Experimental Arthritis.

Watanabe Ishikawa L, Colavite P, de Campos Fraga-Silva T, Mimura L, Franca T, Zorzella-Pezavento S J Immunol Res. 2016; 2016:6765134.

PMID: 27294161 PMC: 4887641. DOI: 10.1155/2016/6765134.

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