Circulating Follicular Helper-Like T Cells in Systemic Lupus Erythematosus

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240
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article
Data de publicação
2015
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WILEY-BLACKWELL
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ARTHRITIS & RHEUMATOLOGY, v.67, n.4, p.988-999, 2015
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Objective. To assess circulating follicular helper T (Tfh)-like CD4+ T cells in patients with systemic lupus erythematosus (SLE) and determine their relationship to disease activity. Methods. Blood samples from patients with SLE, as well as blood samples from patients with Behcet's disease (BD) and healthy individuals as controls, were analyzed. In all samples, circulating Tfh-like cells were enumerated by flow cytometry, using, as markers, expression of CXCR5, inducible T cell costimulator (ICOS), and programmed death 1 (PD-1) protein, as well as secretion of interleukin-21 (IL-21). The frequency of circulating Tfh-like cells was compared to that of circulating plasmablasts (CD19+IgD-CD38+). In addition, the possible association of circulating Tfh-like cells with the SLE Disease Activity Index (SLEDAI) was evaluated. Results. The subset of circulating Tfh-like T cells, identified as CXCR5(high)ICOS(high)PD-1(high), was expanded in the blood of SLE patients compared to controls. Circulating Tfh-like cells were found to produce IL-21 and had lower expression of CCR7 as compared to that in circulating CXCR5(high) central memory T cells, thereby enabling their distinction. Expression of PD-1, but not ICOS or CXCR5, was significantly elevated in circulating Tfh-like cells from SLE patients compared to controls. PD-1 expression among CXCR5(high) circulating Tfh-like cells correlated with the SLEDAI, frequency of circulating plasmablasts, and anti-double-stranded DNA antibody positivity, but not with disease duration or past organ injury; rather, this cell profile appeared to be a reflection of current active disease. Conclusion. Circulating Tfh-like cells are associated with disease activity in SLE, suggesting that their presence indicates abnormal homeostasis of T cell-B cell collaboration, with a causal relationship that is central to disease pathogenesis. These findings also suggest that circulating Tfh-like cells provide a surrogate for aberrant germinal center activity in SLE, and that their PD-1 expression offers a tool for measuring disease activity and monitoring the response to therapies.
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Referências
  1. Anolik J, 2004, CURR OPIN RHEUMATOL, V16, P505, DOI 10.1097/01.bor.0000133660.52599.f6
  2. Arce E, 2001, J IMMUNOL, V167, P2361
  3. Baechler EC, 2003, P NATL ACAD SCI USA, V100, P2610, DOI 10.1073/pnas.0337679100
  4. Bengtsson AA, 2000, LUPUS, V9, P664, DOI 10.1191/096120300674499064
  5. Bentebibel SE, 2011, P NATL ACAD SCI USA, V108, pE488, DOI 10.1073/pnas.1100898108
  6. Bentebibel SE, 2013, SCI TRANSL MED, V5, DOI 10.1126/scitranslmed.3005191
  7. Breitfeld D, 2000, J EXP MED, V192, P1545, DOI 10.1084/jem.192.11.1545
  8. Burmeister Y, 2008, J IMMUNOL, V180, P774
  9. Cappione A, 2005, J CLIN INVEST, V115, P3205, DOI 10.1172/JCI24179
  10. Chang A, 2011, J IMMUNOL, V186, P1849, DOI 10.4049/jimmunol.1001983
  11. Chevalier N, 2011, J IMMUNOL, V186, P5556, DOI 10.4049/jimmunol.1002828
  12. Choi YS, 2011, IMMUNITY, V34, P932, DOI 10.1016/j.immuni.2011.03.023
  13. Craft JE, 2012, NAT REV RHEUMATOL, V8, P337, DOI 10.1038/nrrheum.2012.58
  14. SILMAN AJ, 1990, LANCET, V335, P1078
  15. Dorner T, 2004, LUPUS, V13, P283, DOI 10.1191/0961203304lu1014oa
  16. Dorner T, 2011, ARTHRITIS RES THER, V13, DOI 10.1186/ar3433
  17. Ettinger R, 2005, J IMMUNOL, V175, P7867
  18. Ferreiros-Vidal I, 2007, GENES IMMUN, V8, P138, DOI 10.1038/sj.gene.6364370
  19. Francisco LM, 2010, IMMUNOL REV, V236, P219, DOI 10.1111/j.1600-065X.2010.00923.x
  20. Good-Jacobson KL, 2010, NAT IMMUNOL, V11, P535, DOI 10.1038/ni.1877
  21. Grammer AC, 2003, J CLIN INVEST, V112, P1506, DOI 10.1172/JCI200319301
  22. Hale JS, 2013, IMMUNITY, V38, P805, DOI 10.1016/j.immuni.2013.02.020
  23. Haymaker C, 2012, ONCOIMMUNOLOGY, V1, P735, DOI 10.4161/onci.20823
  24. He J, 2013, IMMUNITY, V39, P770, DOI 10.1016/j.immuni.2013.09.007
  25. Jacobi AM, 2008, ARTHRITIS RHEUM-US, V58, P1762, DOI 10.1002/art.23498
  26. Johnston RJ, 2009, SCIENCE, V325, P1006, DOI 10.1126/science.1175870
  27. Kasagi S, 2010, J IMMUNOL, V184, P2337, DOI 10.4049/jimmunol.0901652
  28. Kawamoto M, 2006, ARTHRITIS RES THER, V8, DOI 10.1186/ar1928
  29. Kirou KA, 2005, ARTHRITIS RHEUM, V52, P1491, DOI 10.1002/art.21031
  30. Le Coz C, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0075319
  31. Le Bon A, 2001, IMMUNITY, V14, P461, DOI 10.1016/S1074-7613(01)00126-1
  32. Linterman MA, 2010, J EXP MED, V207, P353, DOI 10.1084/jem.20091738
  33. Linterman MA, 2009, J EXP MED, V206, P561, DOI 10.1084/jem.20081886
  34. Liu JL, 2009, J EUR ACAD DERMATOL, V23, P425, DOI 10.1111/j.1468-3083.2009.03087.x
  35. Locci M, 2013, IMMUNITY, V39, P758, DOI 10.1016/j.immuni.2013.08.031
  36. Luzina IG, 2001, J LEUKOCYTE BIOL, V70, P578
  37. Mendes D, 2009, J AUTOIMMUN, V32, P178, DOI 10.1016/j.jaut.2009.02.011
  38. Morita R, 2011, IMMUNITY, V34, P108, DOI 10.1016/j.immuni.2010.12.012
  39. Nurieva RI, 2009, SCIENCE, V325, P1001, DOI 10.1126/science.1176676
  40. Odegard JM, 2008, J EXP MED, V205, P2873, DOI 10.1084/jem.20080840
  41. Pepper M, 2011, IMMUNITY, V35, P583, DOI 10.1016/j.immuni.2011.09.009
  42. Petri M, 2007, ANN RHEUM DIS, V66, P61, DOI 10.1136/ard.2007.078477
  43. Ray JP, 2014, IMMUNITY, V40, P367, DOI 10.1016/j.immuni.2014.02.005
  44. Sallusto F, 1999, NATURE, V401, P708, DOI 10.1038/44385
  45. Schaerli P, 2000, J EXP MED, V192, P1553, DOI 10.1084/jem.192.11.1553
  46. Shah K, 2010, ARTHRITIS RES THER, V12, DOI 10.1186/ar2964
  47. SHLOMCHIK MJ, 1987, P NATL ACAD SCI USA, V84, P9150, DOI 10.1073/pnas.84.24.9150
  48. Simpson N, 2010, ARTHRITIS RHEUM-US, V62, P234, DOI 10.1002/art.25032
  49. TAN EM, 1982, ARTHRITIS RHEUM, V25, P1271, DOI 10.1002/art.1780251101
  50. Terawaki S, 2011, J IMMUNOL, V186, P2772, DOI 10.4049/jimmunol.1003208
  51. Terrier B, 2012, J RHEUMATOL, V39, P1819, DOI 10.3899/jrheum.120468
  52. Vinuesa CG, 2005, NATURE, V435, P452, DOI 10.1038/nature03555
  53. Vinuesa CG, 2009, NAT REV IMMUNOL, V9, P845, DOI 10.1038/nri2637
  54. Watanabe T, 2010, J VIRAL HEPATITIS, V17, P453, DOI 10.1111/j.1365-2893.2010.01313.x
  55. Weinstein JS, 2014, J IMMUNOL, V192, P3166, DOI 10.4049/jimmunol.1302617
  56. William J, 2002, SCIENCE, V297, P2066, DOI 10.1126/science.1073924
  57. Yu D, 2009, IMMUNITY, V31, P457, DOI 10.1016/j.immuni.2009.07.002
  58. Zotos D, 2010, J EXP MED, V207, P365, DOI 10.1084/jem.20091777