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

Joshua J. Michel, Carl Turesson, Bonnie Lemster, Sarah R. Atkins, Cristina Iclozan, Tim Bongartz, Mary Chester Wasko, Eric Lawrence Matteson, Abbe N. Vallejo

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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) α/β-chain usage and restricted TCR third complementarity-determining region spectra. Histologic studies showed that CD56+ T cells were components of cellular infiltrates in RA-associated IP. CD56 crosslinking on T cells sufficiently induced cytokine production, although CB56/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.

Original languageEnglish (US)
Pages (from-to)43-57
Number of pages15
JournalArthritis and Rheumatism
Volume56
Issue number1
DOIs
StatePublished - Jan 2007

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Rheumatoid Arthritis
T-Lymphocytes
T-Cell Antigen Receptor
Null Lymphocytes
Interstitial Lung Diseases
Leukocytes
Complementarity Determining Regions
Cell Aging
Cellular Structures
Biological Assay
Flow Cytometry
Joints
Immunohistochemistry
Cytokines
Phenotype
Biopsy
Lung

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Michel, J. J., Turesson, C., Lemster, B., Atkins, S. R., Iclozan, C., Bongartz, T., ... Vallejo, A. N. (2007). CD56-expressing T cells that have features of senescence are expanded in rheumatoid arthritis. Arthritis and Rheumatism, 56(1), 43-57. https://doi.org/10.1002/art.22310

CD56-expressing T cells that have features of senescence are expanded in rheumatoid arthritis. / Michel, Joshua J.; Turesson, Carl; Lemster, Bonnie; Atkins, Sarah R.; Iclozan, Cristina; Bongartz, Tim; Wasko, Mary Chester; Matteson, Eric Lawrence; Vallejo, Abbe N.

In: Arthritis and Rheumatism, Vol. 56, No. 1, 01.2007, p. 43-57.

Research output: Contribution to journalArticle

Michel, JJ, Turesson, C, Lemster, B, Atkins, SR, Iclozan, C, Bongartz, T, Wasko, MC, Matteson, EL & Vallejo, AN 2007, 'CD56-expressing T cells that have features of senescence are expanded in rheumatoid arthritis', Arthritis and Rheumatism, vol. 56, no. 1, pp. 43-57. https://doi.org/10.1002/art.22310
Michel JJ, Turesson C, Lemster B, Atkins SR, Iclozan C, Bongartz T et al. CD56-expressing T cells that have features of senescence are expanded in rheumatoid arthritis. Arthritis and Rheumatism. 2007 Jan;56(1):43-57. https://doi.org/10.1002/art.22310
Michel, Joshua J. ; Turesson, Carl ; Lemster, Bonnie ; Atkins, Sarah R. ; Iclozan, Cristina ; Bongartz, Tim ; Wasko, Mary Chester ; Matteson, Eric Lawrence ; Vallejo, Abbe N. / CD56-expressing T cells that have features of senescence are expanded in rheumatoid arthritis. In: Arthritis and Rheumatism. 2007 ; Vol. 56, No. 1. pp. 43-57.
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abstract = "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) α/β-chain usage and restricted TCR third complementarity-determining region spectra. Histologic studies showed that CD56+ T cells were components of cellular infiltrates in RA-associated IP. CD56 crosslinking on T cells sufficiently induced cytokine production, although CB56/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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AU - Bongartz, Tim

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N2 - 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) α/β-chain usage and restricted TCR third complementarity-determining region spectra. Histologic studies showed that CD56+ T cells were components of cellular infiltrates in RA-associated IP. CD56 crosslinking on T cells sufficiently induced cytokine production, although CB56/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.

AB - 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) α/β-chain usage and restricted TCR third complementarity-determining region spectra. Histologic studies showed that CD56+ T cells were components of cellular infiltrates in RA-associated IP. CD56 crosslinking on T cells sufficiently induced cytokine production, although CB56/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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