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The Dynamics of Articular Leukocyte Trafficking and the Immune Response to Self Heat-Shock Protein 65 Influence Arthritis Susceptibility

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Abstract

Introduction

Adjuvant arthritis (AA) shares several features with human rheumatoid arthritis, and it can be induced in the Lewis (LEW) rat but not the Wistar Kyoto (WKY) rat (both RT.1l) by immunization with heat-killed Mycobacterium tuberculosis (Mtb). We set out to unravel the mechanisms underlying the differential susceptibility to AA of these MHC-compatible rat strains.

Materials and Methods

We compared the levels of T-cell proliferative and cytokine response to the immunoregulatory self (rat) hsp65 (Rhsp65) after an arthritogenic (Mtb) challenge and the kinetics of migration of adoptively transferred, 111Indium-labeled, Mtb-primed leukocytes into the hind paw joints of recipient rats.

Results and Discussion

The WKY rats raised a significantly higher level of T-cell proliferative response coupled with a temporally opposite cytokine profile against the disease-regulating Rhsp65 compared to that of LEW rats. Moreover, the arthritogenic leukocytes accumulated into the joints of WKY rats at significantly lower numbers than that in LEW rats.

Conclusions

These results offer novel insights into the immune events influencing the pathogenesis of autoimmune arthritis.

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Acknowledgment

This work was supported by grants from the Arthritis Foundation (Atlanta, GA, and the Maryland Chapter, Baltimore, MD) and the Maryland Arthritis Research Center (MARRC), Baltimore, MD. We wish to thank Stephen Shaw and Sam Huang from the NIH (Bethesda, MD) and Ron Mease from UMB for their helpful suggestions during the course of this study.

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Author notes

  1. Md. Y. Mia

    Present address: Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Maryland School of Medicine, Howard Hall 323C, 660 West Redwood Street, Baltimore, MD, 21201, USA

    Md. Y. Mia, Eugene Y. Kim, Shailesh R. Satpute & Kamal D. Moudgil

  2. Division of Rheumatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Kamal D. Moudgil

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  1. Md. Y. Mia
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Correspondence to Kamal D. Moudgil.

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Mia, M.Y., Kim, E.Y., Satpute, S.R. et al. The Dynamics of Articular Leukocyte Trafficking and the Immune Response to Self Heat-Shock Protein 65 Influence Arthritis Susceptibility. J Clin Immunol 28, 420–431 (2008). https://doi.org/10.1007/s10875-008-9205-4

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