CD56-expressing T cells that have features of senescence are expanded in rheumatoid arthritis.
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) alpha/beta-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 CD56/TCR coligation induced higher production levels.


CONCLUSIONS
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.
Michel
Joshua J
JJ
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Turesson
Carl
C
Lemster
Bonnie
B
Atkins
Sarah R
SR
Iclozan
Cristina
C
Bongartz
Tim
T
Wasko
Mary Chester
MC
Matteson
Eric L
EL
Vallejo
Abbe N
AN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D001706:Biopsy; D019002:CD56 Antigen / Q000378:metabolism*; D018929:Cell Culture Techniques; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D019002:CD56 Antigen