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

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) ␣/␤-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.

Persistent accumulation of interferon-γ-producing CD8+CD56+ T cells in blood from patients with coronary artery disease

“…As expected, we found a lack of CD28 on the majority of CD8 + CD56 + T cells. The reciprocal expression of CD56 and CD28 on peripheral T cells has been described by several [10][11]17 and is considered an indicator of T cell senescence. Resistance to apoptosis is considered another feature of senescent CD8 + T cells 28 instability.…”

“…In infants, the numbers of circulating CD8 + CD56 + T cells are extremely low, but then increase with age 10 . The induction of CD56 has been shown to correlate with the loss of CD28, a hallmark of immunological aging [10][11] , and furthermore, the conversion to a senescent T cell phenotype is accentuated by a common pathogen, namely cytomegalovirus (CMV) 12 . In addition, increased proportions of circulating CD8 + CD56 + T cells are described in chronic autoimmune diseases like rheumatoid arthritis, sarcoidosis and…”

“…Behcet´s uveitis 11,[13][14][15] . The expression of CD56 on CD8 + T cells has also been associated with disease activity 11,16 .…”

“…The expression of CD56 on CD8 + T cells has also been associated with disease activity 11,16 . Still, the clinical relevance of accumulated CD8 + CD56 + T cells during aging and disease is far from clarified.…”

Pro- and anti-inflammatory actions in coronary artery disease : with focus on CD56+ T cells and Annexin A1

“…Furthermore, the gain of CD56 has been shown to correlate with the loss of CD28, which is a hallmark of immunosenescence (Michel et al, 2007). While CD56 + T cells are potent producers of proinflammatory cytokines, such as IFN-γ and TNF, they seem to be poor producers of IL-10 ( Katchar et al, 2005;KellyRogers et al, 2006).…”