Increased CD4+ T cell infiltrates in rheumatoid arthritis–associated interstitial pneumonitis compared with idiopathic interstitial pneumonitis

Turesson, Carl; Matteson, Eric L.; Colby, Thomas V.; Vuk-Pavlović, Zvezdana; Vassallo, Robert; Weyand, Cornelia M.; Tazelaar, Henry D.; Limper, Andrew H.

doi:10.1002/art.20765

Cited by 84 publications

(68 citation statements)

References 43 publications

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“…Our data show that they populate rheumatoid lesions outside the joint, such as in the lung (Figures 5A and B). We previously reported that the lungs of patients with RA-associated IP are characterized by infiltration of CD4ϩ T cells (28). Our present data further show that such lung-infiltrating cells are also CD56ϩ.…”

Section: Discussionsupporting

confidence: 87%

“…Moreover, the frequency of these cells was also higher in patients with RA-associated IP than in those with idiopathic IP only. We had previously examined these same tissue blocks and reported that CD16ϩ,CD4Ϫ,CD3Ϫ NK cells were rarely found in the lung tissues (28). The present data indicate that the serially positioned CD4ϩ,CD56ϩ,CD3ϩ cells in the lung lesions are T cells.…”

Section: Cd56؉ T Cells Are Oligoclonal Lymphocytes Oligoclonal Cd28-supporting

confidence: 59%

“…All biopsy specimens were analyzed for the copositioning of CD3, CD4, and CD56 staining in consecutive sections. These biopsy specimens were the same specimens analyzed in a previous study (28) in which we found increased CD4ϩ T cell infiltrates in lung tissues of patients with RA-associated IP. In the present study, new serial sections of tissue blocks were analyzed.…”

Section: Methodsmentioning

confidence: 99%

“…Paraffin-embedded sections of lung biopsy specimens were processed for histology as described previously (28). Antibodies to CD3, CD4, and CD56 (Novocastra, Newcastle-uponTyne, UK) and isotype controls (Dako, Glostrup, Denmark) were used according to the manufacturer's specification.…”

Section: Methodsmentioning

confidence: 99%

“…Excess mortality in RA is associated with extraarticular RA manifestations such as IP (33). We previously reported higher levels of CD4ϩ T cell infiltration in the lungs of patients with RA-associated IP than in those of patients with idiopathic IP only (28). We therefore examined the same cohort of patients with lung disease and assessed whether CD56ϩ T cells were also components of the lung cellular infiltrates.…”

Section: Cd56؉ T Cells Are Oligoclonal Lymphocytes Oligoclonal Cd28-mentioning

confidence: 99%

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CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

Michel

Turesson

Lemster

et al. 2007

Arthritis & Rheumatism

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Objective. T cells deficient in CD28 expression have been implicated in the pathogenesis of rheumatoid arthritis (RA). Given that CD28-null T cells are functionally heterogeneous, we undertook this study to screen for novel receptors on these cells.Methods. Seventy-two patients with RA (ages 35-84 years) and 53 healthy persons (32 young controls ages 19-34 years, 21 older controls ages 39-86 years) were recruited. Phenotypes and proliferative capacity of T cells from fresh leukocytes and of long-term cultures were monitored by flow cytometry. Lung biopsy specimens from patients with RA-associated interstitial pneumonitis (IP) were examined by immunohistochemistry. Receptor functionality was assessed by crosslinking bioassays.Results. Chronic stimulation of CD28؉ T cells in vitro yielded progenies that lacked CD28 but that gained CD56. Ex vivo analysis of leukocytes from patients with extraarticular RA showed a higher frequency of CD56؉,CD28-null T cells than in patients with disease confined to the joints or in healthy controls. CD56؉,CD28-null T cells had nil capacity for proliferation, consistent with cellular senescence. CD56؉ T cells had skewed T cell receptor (TCR) ␣/␤-chain usage and restricted TCR third complementarity-determining region spectra. Histologic studies showed that CD56؉ T cells were components of cellular infiltrates in RAassociated IP. CD56 crosslinking on T cells sufficiently induced cytokine production, although CD56/TCR coligation induced higher production levels.Conclusion. Chronic activation of T cells induces counterregulation of CD28 and CD56 expression. The loss of CD28 is accompanied by the gain of CD56 that confers TCR-independent and TCR-dependent activation pathways. We propose that accumulation of CD56؉ T cells in RA contributes to maladaptive immune responses and that CD56؉ T cells are potential targets for therapy.

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Section: Discussionsupporting

confidence: 87%

Section: Cd56؉ T Cells Are Oligoclonal Lymphocytes Oligoclonal Cd28-supporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Cd56؉ T Cells Are Oligoclonal Lymphocytes Oligoclonal Cd28-mentioning

confidence: 99%

See 3 more Smart Citations

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

Michel

Turesson

Lemster

et al. 2007

Arthritis & Rheumatism

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Interstitial lung disease in connective tissue diseases: What are the important questions?

2005

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Morphologic and quantitative assessment of CD20+ B cell infiltrates in rheumatoid arthritis–associated nonspecific interstitial pneumonia and usual interstitial pneumonia

Atkins¹,

Turesson²,

Myers³

et al. 2006

Arthritis & Rheumatism

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Objective. B lymphocytes are emerging as important elements in the events leading to joint destruction in rheumatoid arthritis (RA). However, B lymphocytes have not been studied in rheumatoid arthritis (RA)-associated lung disease. We performed a morphologic and quantitative analysis of B lymphocytes and plasma cells in RA-associated interstitial pneumonia (IP) in comparison with idiopathic IP and normal lungs.Methods. Open-lung biopsy specimens from patients with RA-associated IP (n ‫؍‬ 18), patients with idiopathic IP (n ‫؍‬ 21), and control subjects (n ‫؍‬ 11) were stained with antibodies to CD20 and CD138. Morphologic patterns of stained specimens were characterized and staining was quantified using computerassisted image analysis.Results. In RA-associated IP, marked follicular B cell hyperplasia was detected, which was limited almost entirely to peribronchiolar lymphoid aggregates. Plasma cells were also present in large numbers, but showed a more diffuse Conclusion. We demonstrated a significant follicular B cell hyperplasia in RA-associated IP. The differences between RA-associated IP and idiopathic IP imply a differential emphasis of B cell-mediated mechanisms in the 2 diseases despite radiologic and histologic similarities and provide a rationale for studying functional aspects of B cell involvement in the pathogenesis of RA-associated IP.

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Increased CD4+ T cell infiltrates in rheumatoid arthritis–associated interstitial pneumonitis compared with idiopathic interstitial pneumonitis

Cited by 84 publications

References 43 publications

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

Interstitial lung disease in connective tissue diseases: What are the important questions?

Morphologic and quantitative assessment of CD20+ B cell infiltrates in rheumatoid arthritis–associated nonspecific interstitial pneumonia and usual interstitial pneumonia

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