Arthritis induced by a T-lymphocyte clone that responds to Mycobacterium tuberculosis and to cartilage proteoglycans.

Eden, Willem van; Holoshitz, Joseph; Nevo, Zvi; Frenkel, A.; Klajman, A; Cohen, Irun R.

doi:10.1073/pnas.82.15.5117

Cited by 411 publications

(180 citation statements)

References 19 publications

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“…AIA develops in susceptible rat strains after the injection of FCA (1)(2)(3)(4)(5)(6)(7)(8)(9). The first step in the development of AIA is the production of an immune response to FCA.…”

Section: Discussionmentioning

confidence: 99%

“…Although these 2 models have many clinical similarities, fundamental differences in their pathophysiology and genetic control are clearly evident. AIA is a particularly informative model because it predominantly involves T cell-mediated mechanisms (1)(2)(3)(4)(5)(6)(7)(8), in contrast to CIA, which requires both humoral (14)(15)(16)(17)(18)(19)(20) and cellular immunity (21).…”

mentioning

confidence: 99%

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Nitric oxide production during adjuvant‐induced and collagen‐induced arthritis

Cannon

Openshaw

Hibbs

et al. 1996

Arthritis & Rheumatism

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Objective. To investigate the role of nitric oxide (NO) production and NO synthase (NOS) induction during adjuvant-induced arthritis (AIA) and collageninduced arthritis (CIA) in Dark Agouti rats.Methods. Urinary nitrate excretion and immune NOS (iNOS) messenger RNA (mRNA) expression were measured in the joint, lymph node, spleen, and liver tissues following the induction of either AIA or CIA.Results. Urinary nitrate excretion and iNOS mRNA expression increased substantially during joint inflammation in both models of arthritis. However, the increases in urinary nitrate excretion and iNOS mRNA expression observed in the joint, liver, and spleen tissues during AIA were greater than those observed during CIA, although iNOS induction in the lymph nodes was similar for both models. A prior injection with Mycobacterium bovis heat-shock protein resulted in suppression of arthritis and NO production in AIA, but not in CIA.Conclusion. Differences in NO production during AIA versus CIA are a reflection of the fundamental pathophysiologic differences between these 2 models of arthritis. Thus, NO production in these 2 models could not be merely a nonspecific reaction to the adjuvant injection, nor simply a byproduct of local inflammation in the joint.Adjuvant-induced arthritis (AIA) and collageninduced arthritis (CIA) are different models of experi-..Supported by the VA Medical Research Program, the NIH (grants HL-40665 and HL-37615), the Nora Eccles Treadwell Foundation, and a University of Utah Research Grant.Grant W. Cannon, MD, Scott J. Openshaw, BS, John B. Hibbs, Jr., MD, John R. Hoidal, MD, Thomas P. Huecksteadt, Marie M. Griffiths, PhD: VA Medical Center, and the University of Utah, Salt Lake City.Address correspondence to Grant W. Cannon, MD, VAMC (llE), 500 Foothill Drive, Salt Lake City, UT 84148.Submitted for publication September 11, 1995; accepted in revised form May 1, 1996. mental arthritis that are induced by the injection of Freund's complete adjuvant (FCA) (1-12) or type I1 collagen (CII) (13-21), respectively. Although these 2 models have many clinical similarities, fundamental differences in their pathophysiology and genetic control are clearly evident. AIA is a particularly informative model because it predominantly involves T cell-mediated mechanisms (1-8), in contrast to CIA, which requires both humoral (14-20) and cellular immunity (21).Nitric oxide (NO), an unstable radical produced by the action of the enzyme NO synthase (NOS) on 1.-arginine, is a mediator of multiple physiologic functions and may also mediate local inflammation and tissue destruction (22-25). After its production and local action, NO is eventually oxidized to nitrate, which is inactive and excreted in the urine. Urinary nitrate can be reduced to nitrite, which, when measured by the Griess reaction, serves as an indirect measure of NO production (22). The induction of immunehflammatory NOS (iNOS) messenger RNA (mRNA) can be detected by polymerase chain reaction (PCR).Recent evaluations of NO synthesis in streptococcal cell wall...

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“…AIA develops in susceptible rat strains after the injection of FCA (1)(2)(3)(4)(5)(6)(7)(8)(9). The first step in the development of AIA is the production of an immune response to FCA.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Nitric oxide production during adjuvant‐induced and collagen‐induced arthritis

Cannon

Openshaw

Hibbs

et al. 1996

Arthritis & Rheumatism

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“…Holoshitz and colleagues demonstrated antigenic similarity between a fraction of M tuberculosis and human cartilage ( 14). Those investigators also induced arthritis in rats, using a T lymphocyte clone that recognized both M tuberculosis antigens and antigens in human synovial fluid and cartilage (15). A cellmediated cross-reactive immune response to M tuberculosis might therefore contribute to the inflammatory arthropathy of Poncet's disease.…”

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confidence: 99%

Tuberculous rheumatism (poncet's disease) in a child

Southwood

Hancock

Petty

et al. 1988

Arthritis & Rheumatism

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A 2‐year‐old boy who had increasing difficulty walking and had large, warm, sterile knee and ankle effusions was found to have active vertebral tuberculosis and a large prevertebral abscess. Lymphocyte proliferation assays demonstrated increased purified protein derivative‐induced reactivity of synovial fluid lymphocytes compared with peripheral blood lymphocytes. The arthritis responded rapidly to antituberculous and antiinflammatory drugs. This patient's disease represented an example of tuberculous rheumatism (Poncet's disease).

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“…First, the lack of a strong Th1 response to Hsp65 in these patients suggests that they were unable to mount a proinflammatory immune response to the vaccine antigen; therefore, the development of autoreactivity and/or pathogenic autoimmunity due to crossrecognition of Hsp65 and Hsp60 was unlikely. Second, although in animal models, injection of mycobacterial products can induce proinflammatory autoimmune clones that recognize Hsp65, 30,31 immunization with purified protein or even with DNA-hsp65 itself, seems almost invariably to induce protection against autoimmune disease, 29,30,32 with the possible exception of two highly susceptible animal models. 33,34 Taken together, our results show that, although our measurements were able to detect some degree of immunostimulation by DNA-hsp65, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured.…”

Section: Discussionmentioning

confidence: 99%

Immune response to vaccination with DNA-hsp65 in a phase I clinical trial with head and neck cancer patients

et al. 2009

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DNA-hsp65, a DNA vaccine encoding the 65-kDa heat-shock protein of Mycobacterium leprae (Hsp65) is capable of inducing the reduction of established tumors in mouse models. We conducted a phase I clinical trial of DNA-hsp65 in patients with advanced head and neck carcinoma. In this article, we report on the vaccine's potential to induce immune responses to Hsp65 and to its human homologue, Hsp60, in these patients. Twenty-one patients with unresectable squamous cell carcinoma of the head and neck received three doses of 150, 400 or 600 mg naked DNA-hsp65 plasmid by ultrasound-guided intratumoral injection. Vaccination did not increase levels of circulating anti-hsp65 IgG or IgM antibody, or lead to detectable Hsp65-specific cell proliferation or interferon-g (IFN-g) production by blood mononuclear cells. Frequency of antigen-induced IL-10-producing cells increased after vaccination in 4 of 13 patients analyzed. Five patients showed disease stability or regression following immunization; however, we were unable to detect significant differences between these patients and those with disease progression using these parameters. There was also no increase in antibody or IFN-g responses to human Hsp60 in these patients. Our results suggest that although DNA-hsp65 was able to induce some degree of immunostimulation with no evidence of pathological autoimmunity, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured. Future studies should focus on characterizing more reliable correlations between immune response parameters and clinical outcome that may be used as predictors of vaccine success in immunosuppressed individuals.

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Arthritis induced by a T-lymphocyte clone that responds to Mycobacterium tuberculosis and to cartilage proteoglycans.

Cited by 411 publications

References 19 publications

Nitric oxide production during adjuvant‐induced and collagen‐induced arthritis

Nitric oxide production during adjuvant‐induced and collagen‐induced arthritis

Tuberculous rheumatism (poncet's disease) in a child

Immune response to vaccination with DNA-hsp65 in a phase I clinical trial with head and neck cancer patients

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