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 language | English (US) |
|---|---|
| Pages (from-to) | 43-57 |
| Number of pages | 15 |
| Journal | Arthritis and Rheumatism |
| Volume | 56 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2007 |
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ASJC Scopus subject areas
- Immunology
- Rheumatology
Cite this
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 journal › Article
}
TY - JOUR
T1 - CD56-expressing T cells that have features of senescence are expanded in rheumatoid arthritis
AU - Michel, Joshua J.
AU - Turesson, Carl
AU - Lemster, Bonnie
AU - Atkins, Sarah R.
AU - Iclozan, Cristina
AU - Bongartz, Tim
AU - Wasko, Mary Chester
AU - Matteson, Eric Lawrence
AU - Vallejo, Abbe N.
PY - 2007/1
Y1 - 2007/1
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.
UR - http://www.scopus.com/inward/record.url?scp=33846197453&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846197453&partnerID=8YFLogxK
U2 - 10.1002/art.22310
DO - 10.1002/art.22310
M3 - Article
C2 - 17195207
AN - SCOPUS:33846197453
VL - 56
SP - 43
EP - 57
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 1
ER -