Collagen-specific T-cell repertoire in blood and synovial fluid varies with disease activity in early rheumatoid arthritis

Ria, Francesco; Penitente, Romina; Santis, Maria De; Nicolò, Chiara; Sante, Gabriele Di; Orsini, Massimiliano; Arzani, Dario; Fattorossi, Andrea; Battaglia, Alessandra; Ferraccioli, Gianfranco

doi:10.1186/ar2553

Cited by 39 publications

(53 citation statements)

References 48 publications

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“…Similarly, we have shown that T cell repertoires are different in pathogenic and nonpathogenic autoimmune responses in human disease and experimental models (40,46). We therefore asked if cell localization ( H PE-⌬MPT64-BCG versus H ⌬MPT64-BCG) and amount of antigen produced ( H PE-⌬MPT64-BCG versus 33 PE-⌬MPT64-BCG) impact T cell repertoire selection and if differences in the composition of the MPT64-specific repertoire were correlated with protection.…”

Section: Pe-⌬mpt64-bcg Correlates With the Induction Of Ifn-␥ Expressmentioning

confidence: 98%

Surface Expression of MPT64 as a Fusion with the PE Domain of PE_PGRS33 EnhancesMycobacterium bovisBCG Protective Activity againstMycobacterium tuberculosisin Mice

Sali¹,

Sante²,

Cascioferro

et al. 2010

Infect Immun

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To improve the current vaccine against tuberculosis, a recombinant strain of Mycobacterium bovis bacillus Calmette-Guérin (rBCG) expressing a Mycobacterium tuberculosis vaccine candidate antigen (MPT64) in strong association with the mycobacterial cell wall was developed. To deliver the candidate antigen on the surface, we fused the mpt64 gene to the sequence encoding the PE domain of the PE_PGRS33 protein of M. tuberculosis (to create strain H PE-⌬MPT64-BCG), which we have previously shown to transport proteins to the bacterial surface. In a series of protection experiments in the mouse model of tuberculosis, we showed that (i) immunization of mice with H PE-⌬MPT64-BCG provides levels of protection significantly higher than those afforded by the parental BCG strain, as assessed by bacterial colonization in lungs and spleens and by lung involvement

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Section: Pe-⌬mpt64-bcg Correlates With the Induction Of Ifn-␥ Expressmentioning

confidence: 98%

Surface Expression of MPT64 as a Fusion with the PE Domain of PE_PGRS33 EnhancesMycobacterium bovisBCG Protective Activity againstMycobacterium tuberculosisin Mice

Sali¹,

Sante²,

Cascioferro

et al. 2010

Infect Immun

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“…A temporal analysis of the expression of cytokines showed that TNF-α was increased in the synovial lining starting from day 11, and in macrophages starting from day 18, whereas IL-6 appeared in the synovial lining, macrophages and endothelium from day 7. mRNA levels for the three cytokines were similarly upregulated at the time of the appearance of joint swelling (day 10); however, TNF-α and IL-1β levels peaked later (day 20 and day 16, respectively) than IL-6 (day [12][13][14]. Synovial protein levels appeared from day 4 for IL-6, day 10 for TNF-α and day 18 for IL-1β.…”

Section: Adjuvant-induced Arthritismentioning

confidence: 99%

“…Collagen type II is one possible candidate autoantigen in human RA, and it stimulates specific clonotypes that occur in the beginning of the early phases of RA and during relapses of longstanding RA (14). The data implicating collagen type II as an autoantigen came from the occurrence of arthritis in an animal model, the collagen-induced arthritis (CIA) model.…”

Section: Collagen-induced Arthritismentioning

confidence: 99%

Interleukin-1β and Interleukin-6 in Arthritis Animal Models: Roles in the Early Phase of Transition from Acute to Chronic Inflammation and Relevance for Human Rheumatoid Arthritis

Ferraccioli

Bracci-Laudiero

Alivernini

et al. 2010

Mol Med

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Tumor necrosis factor-α (TNF-α) is the major target of the therapeutic approach in rheumatoid arthritis. A key issue in the approach to chronic arthritis is the understanding of the crucial molecules driving the transition from the acute phase to the chronic irreversible phase of the disease. In this review we analyzed five experimental arthritis animal models (antigen-induced arthritis, adjuvant-induced arthritis, streptococcal cell wall arthritis, collagen-induced arthritis and SKG) considered as possible scenarios to facilitate interpretation of the biology of human rheumatoid arthritis. The SKG model is strictly dependent on interleukin (IL)-6. In the other models, IL-1β and IL-6, more than TNF-α, appear to be relevant in driving the transition, which suggests that these should be the targets of an early intervention to stop the course toward the chronic form of the disease.

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“…First, an appropriate T cell repertoire has to be activated. In fact, activated self-reactive T cells of healthy and sick individuals belong to distinct repertoires in both experimental and human autoimmune diseases (6,7). Second, polarization of T cells toward a pathogenic phenotype needs to be induced.…”

mentioning

confidence: 99%

Mycobacterium smegmatisExpressing a Chimeric Protein MPT64-Proteolipid Protein (PLP) 139–151 Reorganizes the PLP-Specific T Cell Repertoire Favoring a CD8-Mediated Response and Induces a Relapsing Experimental Autoimmune Encephalomyelitis

Nicolò¹,

Sali

Sante³

et al. 2009

The Journal of Immunology

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We infected SJL mice with a recombinant Mycobacterium smegmatis expressing a chimeric protein containing the self-epitope of proteolipid protein 139–151 (p139) fused to MPT64, a secreted protein of Mycobacterium tuberculosis (rMSp139). Infected mice developed a relapsing experimental autoimmune encephalomyelitis (EAE), showing a prevailing demyelination of the CNS, and disease severity was significantly lower in comparison with the one that follows immunization with p139. rMSp139 was not detected in lymph node or spleen in the course of clinical disease development or in the CNS during relapse. Infection with rMSp139 modified the p139-specific T cell repertoire, recruiting the spontaneous p139-specific repertoire and activating CD4+ T cells carrying the BV4 semiprivate rearrangement. T cells carrying the public BV10 rearrangement that are consistently found in the CNS during flares of disease were not activated by infection with rMSp139 because lymph node APCs infected with rMSp139 selectively fail to present the epitope for which BV10 cells are specific. Simultaneously, rMSp139 expanded p139-specific CD8+ cells more efficiently than immunization with peptide in adjuvant. SJL mice vaccinated against the CDR3 sequence of the BV10 public rearrangement reduced usage of the BV10 cells and displayed reduced symptoms during bouts of EAE. Thus, transient peripheral infection with a CNS-cross–reactive nonpathogenic Mycobacterium induces a relapsing EAE that continues long after clearance of the infectious agent. The composition of the self-reactive repertoire activated determines severity and histology of the resulting disease.

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Collagen-specific T-cell repertoire in blood and synovial fluid varies with disease activity in early rheumatoid arthritis

Abstract: Introduction Type II collagen is a DR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis. The aim of the present study was to analyze the T-cell receptor repertoire at the onset of and at different phases in rheumatoid arthritis.

Cited by 39 publications

References 48 publications

Surface Expression of MPT64 as a Fusion with the PE Domain of PE_PGRS33 EnhancesMycobacterium bovisBCG Protective Activity againstMycobacterium tuberculosisin Mice

Surface Expression of MPT64 as a Fusion with the PE Domain of PE_PGRS33 EnhancesMycobacterium bovisBCG Protective Activity againstMycobacterium tuberculosisin Mice

Interleukin-1β and Interleukin-6 in Arthritis Animal Models: Roles in the Early Phase of Transition from Acute to Chronic Inflammation and Relevance for Human Rheumatoid Arthritis

Mycobacterium smegmatisExpressing a Chimeric Protein MPT64-Proteolipid Protein (PLP) 139–151 Reorganizes the PLP-Specific T Cell Repertoire Favoring a CD8-Mediated Response and Induces a Relapsing Experimental Autoimmune Encephalomyelitis

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