T cell responses to human type II collagen in patients with rheumatoid arthritis and healthy controls

Snowden, Neil; Reynolds, I.; Morgan, K; Holt, Lennox

doi:10.1002/art.4

Cited by 9 publications

(11 citation statements)

References 42 publications

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“…Second, accelerated T cell responses to GPIIb-IIIa in ITP patients indicate recent antigen exposure or in vivo activation of T cells, whereas kinetics of modified GPIIb-IIIa-induced T cell responses in healthy donors are more typical of those of naive T cell responses (32). Similar differences in kinetics of autoantigen-specific T cell proliferation in patients versus healthy individuals were shown in T cell responses to type II collagen in rheumatoid arthritis (33) and to topoisomerase I in scleroderma (8).…”

Section: Discussionmentioning

confidence: 87%

Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody.

Kuwana¹,

Kaburaki²,

Ikeda³

1998

J. Clin. Invest.

213

173

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T cell proliferative responses to platelet membrane GPIIbIIIa were examined in 14 patients with chronic immune thrombocytopenic purpura (ITP), 7 systemic lupus erythematosus (SLE) patients with or without thrombocytopenia, and 10 healthy donors. Although peripheral blood T cells from all subjects failed to respond to the protein complex in its native state, reduced GPIIb-IIIa stimulated T cells from three ITP patients and one SLE patient with thrombocytopenia, and tryptic peptides of GPIIb-IIIa stimulated T cells from nearly all subjects. The specificity of the responses for GPIIb-IIIa was confirmed by activation of GPIIb-IIIa-primed T cells by a recombinant GPIIb ␣ fragment in secondary cultures. Characterization of T cell response induced by modified GPIIb-IIIa showed that the response was restricted by HLA-DR, the responding T cells had a CD4

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Section: Discussionmentioning

confidence: 87%

Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody.

Kuwana¹,

Kaburaki²,

Ikeda³

1998

J. Clin. Invest.

213

173

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“…In addition to reports showing that transgenic expression of DR4 and DR1 in mice permits development of CIA (2,3,27), there are several investigations describing T cell immunity to CII in either healthy individuals or RA patients or both (5,(28)(29)(30)(31)(32)(33)(34)(35)(36). However, less is known regarding the determinants recognized by CII-specific T cells in humans, and the interpretations of the reported findings are not all in agreement (4,5,34,35).…”

Section: Discussionmentioning

confidence: 97%

“…However, less is known regarding the determinants recognized by CII-specific T cells in humans, and the interpretations of the reported findings are not all in agreement (4,5,34,35). For example, one recent study failed to identify CII-specific T cells in RA patients when CII259-272 loaded DR4-tetramers were used (4), despite the earlier defined immunodominance of this peptide in DR4-transgenic mice (1).…”

Section: Discussionmentioning

confidence: 99%

Predominant selection of T cells specific for the glycosylated collagen type II epitope (263–270) in humanized transgenic mice and in rheumatoid arthritis

Bäcklund

Carlsén

Höger

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

192

194

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Rheumatoid arthritis (RA) is associated with certain MHC class II alleles and is characterized by a chronic autoimmune response in the joints. Using transgenic mice expressing human DR4 (DRB1*0401) and human CD4, but lacking endogenous MHC class II, we show that posttranslational glycosylation of type II collagen (CII) influences the level of T cell tolerance to this candidate cartilage-specific autoantigen. In such mice, the expression of human CII resulted in a tolerized murine T cell response to human CII. However, tolerance induction remained incomplete, preferentially deleting responses to the nonmodified CII 263-270 epitope, whereas T cell recognition of a glycosylated variant of this epitope was affected to a lesser degree. A similar dominance of T cell responses to CII-glycopeptides was recorded in a cohort of severely affected RA-patients (n ‫؍‬ 14). Thus, RA T cells predominantly recognize the immunodominant CII peptide in its glycosylated form and may explain why previously it has been difficult to detect T cell responses to CII in RA patients.

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“…Anti-CII autoantibodies are important players in this collagen-induced arthritis (CIA). They are also found in the blood and joints in RA (8,9), whereas CII-specific T cells have been difficult to demonstrate in either compartment (10,11). However, conducting this search mainly in patients with long durations of both RA and immunosuppressive drug treatments probably biases against detection of the T cells that initiate the disease process, which may well be rare and/or short-lived.…”

Section: Deraamentioning

confidence: 99%

Tracking of Proinflammatory Collagen-Specific T Cells in Early and Late Collagen-Induced Arthritis in Humanized Mice

Svendsen

Andersen

Willcox

et al. 2004

The Journal of Immunology

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Rheumatoid arthritis is a chronic inflammatory disease associated with certain HLA-DR4 subtypes. The target autoantigen(s) is unknown, but type II collagen (CII) is a candidate, with a single immunodominant DR4-restricted 261–273 T cell epitope (CII(261–273)). In the present study, we have prepared HLA-DR4:CII(261–273) tetramers and analyzed peripheral blood, lymph node, and synovial fluid cells from DR4-transgenic mice with early and late collagen-induced arthritis to draw a fuller picture of the role of CII-reactive Th cells in disease development. Their frequencies increased ∼20-fold in blood 1–2 wk postimmunization, and even more in acutely arthritic joints. Our data strongly suggest that CII-specific Th cells are necessary, but not sufficient for collagen-induced arthritis. The CII-specific Th cells displayed an activated proinflammatory Th1 phenotype, and their expansion correlated with onset and severity of arthritis and also with anti-CII Ab levels. Surprisingly, shortly after the first clinical signs of arthritis, activated HLA-DR4:CII tetramer+ cells became undetectable in the synovial fluid and rare in the blood, but persisted in lymph nodes. Consequently, future human studies should focus on patients with early arthritis, and on their synovial cells, to re-evaluate the occurrence and pathogenic importance of CII-specific or other Th cells in rheumatoid arthritis.

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T cell responses to human type II collagen in patients with rheumatoid arthritis and healthy controls

Cited by 9 publications

References 42 publications

Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody.

Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody.

Predominant selection of T cells specific for the glycosylated collagen type II epitope (263–270) in humanized transgenic mice and in rheumatoid arthritis

Tracking of Proinflammatory Collagen-Specific T Cells in Early and Late Collagen-Induced Arthritis in Humanized Mice

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