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. 2004 Aug;13(4):247–253. doi: 10.1080/09629350400003167

Tc1/Tc2 ratio in the inflammatory process in patients with Behçet's disease.

Habib Houman 1, Agnes Hamzaoui 1, Imed Ben Ghorbal 1, Monia Smiti Khanfir 1, Moncef Feki 1, Kamel Hamzaoui 1
PMCID: PMC1781571  PMID: 15545055

Abstract

BACKGROUND: Peripheral blood CD8+ T cells expressing interferon gamma and interleukin-4 (IL-4), and lacking CD28 molecules, were responsible for the dynamic interplay between peripheral blood and inflammatory sites. INTRODUCTION: The aim of the current study was to define in Behçet's disease (BD), CD8+ T-cell subsets using CD28 and CD11b monoclonal antibodies, and the characterization of the Tc1/Tc2 ratio and perforin expression. METHODS: Flow cytometry was used for intracytoplasmic cytokines and perforin expression. Effector cells were investigated by adhesion of CD8+ T cells to human microvascular endothelial cells and by chemotaxis using beta-chemokine. RESULTS: Interferon-gamma-producing CD8+ T cells in active and remission BD patients were increased, which induce a significant increase of the Tc1:Tc2 ratio in BD. CD8(+)CD28(-)CD11b+ T cells were found to be more expanded in BD patients than in age-matched healthy controls. The expression of CD11b molecules in active BD allowed to CD8(+)CD28+/CD8(+)CD28- subsets to adhere to human microvascular endothelial cells, with more efficiency in BD. Using MIP-1alpha, we observed that the migratory process of CD28(-)CD11b(+) is more important in BD. CD28(-)CD11b+ exhibited an increased perforin expression in BD patients. CONCLUSION: Taken together these results suggest the presence of immune activation, probably in response to a profound inflammation affecting BD patients. The physiopathological significance of these results were toward autoimmune diseases and/or infectious process.

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Selected References

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  1. Arosa Fernando A. CD8+CD28- T cells: certainties and uncertainties of a prevalent human T-cell subset. Immunol Cell Biol. 2002 Feb;80(1):1–13. doi: 10.1046/j.1440-1711.2002.01057.x. [DOI] [PubMed] [Google Scholar]
  2. Borthwick N. J., Bofill M., Gombert W. M., Akbar A. N., Medina E., Sagawa K., Lipman M. C., Johnson M. A., Janossy G. Lymphocyte activation in HIV-1 infection. II. Functional defects of CD28- T cells. AIDS. 1994 Apr;8(4):431–441. doi: 10.1097/00002030-199404000-00004. [DOI] [PubMed] [Google Scholar]
  3. Borthwick N. J., Lowdell M., Salmon M., Akbar A. N. Loss of CD28 expression on CD8(+) T cells is induced by IL-2 receptor gamma chain signalling cytokines and type I IFN, and increases susceptibility to activation-induced apoptosis. Int Immunol. 2000 Jul;12(7):1005–1013. doi: 10.1093/intimm/12.7.1005. [DOI] [PubMed] [Google Scholar]
  4. Butcher E. C. Warner-Lambert/Parke-Davis Award lecture. Cellular and molecular mechanisms that direct leukocyte traffic. Am J Pathol. 1990 Jan;136(1):3–11. [PMC free article] [PubMed] [Google Scholar]
  5. Callan M. F., Tan L., Annels N., Ogg G. S., Wilson J. D., O'Callaghan C. A., Steven N., McMichael A. J., Rickinson A. B. Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus In vivo. J Exp Med. 1998 May 4;187(9):1395–1402. doi: 10.1084/jem.187.9.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Caruso A., Fiorentini S., Licenziati S., Alessandri G., Ricotta D., Imberti L., Signorini S., Armenta-Solis A., Garrafa E., Balsari A. Expansion of rare CD8+ CD28- CD11b- T cells with impaired effector functions in HIV-1-infected patients. J Acquir Immune Defic Syndr. 2000 Aug 15;24(5):465–474. doi: 10.1097/00126334-200008150-00012. [DOI] [PubMed] [Google Scholar]
  7. Direskeneli H. Behçet's disease: infectious aetiology, new autoantigens, and HLA-B51. Ann Rheum Dis. 2001 Nov;60(11):996–1002. doi: 10.1136/ard.60.11.996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Direskeneli H., Saruhan-Direskeneli G. The role of heat shock proteins in Behçet's disease. Clin Exp Rheumatol. 2003 Jul-Aug;21(4 Suppl 30):S44–S48. [PubMed] [Google Scholar]
  9. Effros R. B., Allsopp R., Chiu C. P., Hausner M. A., Hirji K., Wang L., Harley C. B., Villeponteau B., West M. D., Giorgi J. V. Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. AIDS. 1996 Jul;10(8):F17–F22. doi: 10.1097/00002030-199607000-00001. [DOI] [PubMed] [Google Scholar]
  10. Effros R. B., Boucher N., Porter V., Zhu X., Spaulding C., Walford R. L., Kronenberg M., Cohen D., Schächter F. Decline in CD28+ T cells in centenarians and in long-term T cell cultures: a possible cause for both in vivo and in vitro immunosenescence. Exp Gerontol. 1994 Nov-Dec;29(6):601–609. doi: 10.1016/0531-5565(94)90073-6. [DOI] [PubMed] [Google Scholar]
  11. Eglin R. P., Lehner T., Subak-Sharpe J. H. Detection of RNA complementary to herpes-simplex virus in mononuclear cells from patients with Behçet's syndrome and recurrent oral ulcers. Lancet. 1982 Dec 18;2(8312):1356–1361. doi: 10.1016/s0140-6736(82)91268-5. [DOI] [PubMed] [Google Scholar]
  12. Fiorentini S., Licenziati S., Alessandri G., Castelli F., Caligaris S., Bonafede M., Grassi M., Garrafa E., Balsari A., Turano A. CD11b expression identifies CD8+CD28+ T lymphocytes with phenotype and function of both naive/memory and effector cells. J Immunol. 2001 Jan 15;166(2):900–907. doi: 10.4049/jimmunol.166.2.900. [DOI] [PubMed] [Google Scholar]
  13. Gamberg Jane, Pardoe Ingrid, Bowmer M. Ian, Howley Constance, Grant Michael. Lack of CD28 expression on HIV-specific cytotoxic T lymphocytes is associated with disease progression. Immunol Cell Biol. 2004 Feb;82(1):38–46. doi: 10.1111/j.1440-1711.2004.01204.x. [DOI] [PubMed] [Google Scholar]
  14. Griffiths G. M. The cell biology of CTL killing. Curr Opin Immunol. 1995 Jun;7(3):343–348. doi: 10.1016/0952-7915(95)80108-1. [DOI] [PubMed] [Google Scholar]
  15. Hamzaoui A., Ghraïri H., Ammar J., Zekri S., Guemira F., Hamzaoui K. IL-18 mRNA expression and IFN-gamma induction in bronchoalveolar lavage from Behçet's disease. Clin Exp Rheumatol. 2003 Jul-Aug;21(4 Suppl 30):S8–14. [PubMed] [Google Scholar]
  16. Hamzaoui A., Hamzaoui K., Kooli C., Chabbou A., Hentati F., Ayed K. High levels of bcl-2 protein in the T lymphocytes of patients with Behçet's disease. Clin Exp Rheumatol. 1996 Jan-Feb;14(1):106–107. [PubMed] [Google Scholar]
  17. Hamzaoui K., Hamzaoui A., Zakraoui L., Chabbou A. Expression of Bcl-2 in inflammatory sites from patients with active Behçet's disease. Mediators Inflamm. 1999;8(2):101–106. doi: 10.1080/09629359990595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hamzaoui K., Hamzaoui A., Zakraoui L., Chabbou A. Levels of soluble Fas/APO-1 in patients with Behçet's disease. Mediators Inflamm. 1998;7(2):111–114. doi: 10.1080/09629359891261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hamzaoui K., Kahan A., Ayed K., Hamza M. Cytotoxic T cells against herpes simplex virus in Behçet's disease. Clin Exp Immunol. 1990 Sep;81(3):390–395. doi: 10.1111/j.1365-2249.1990.tb05344.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hamzaoui Kamel, Hamzaoui Agnes, Guemira Fethi, Bessioud Moncef, Hamza M'hamed, Ayed Khaled. Cytokine profile in Behçet's disease patients. Relationship with disease activity. Scand J Rheumatol. 2002;31(4):205–210. doi: 10.1080/030097402320318387. [DOI] [PubMed] [Google Scholar]
  21. Hartung A. D., Bohnert A., Hackstein H., Ohly A., Schmidt K. L., Bein G. Th2-mediated atopic disease protection in Th1-mediated rheumatoid arthritis. Clin Exp Rheumatol. 2003 Jul-Aug;21(4):481–484. [PubMed] [Google Scholar]
  22. Hislop A. D., Gudgeon N. H., Callan M. F., Fazou C., Hasegawa H., Salmon M., Rickinson A. B. EBV-specific CD8+ T cell memory: relationships between epitope specificity, cell phenotype, and immediate effector function. J Immunol. 2001 Aug 15;167(4):2019–2029. doi: 10.4049/jimmunol.167.4.2019. [DOI] [PubMed] [Google Scholar]
  23. Hooper M., Kallas E. G., Coffin D., Campbell D., Evans T. G., Looney R. J. Cytomegalovirus seropositivity is associated with the expansion of CD4+CD28- and CD8+CD28- T cells in rheumatoid arthritis. J Rheumatol. 1999 Jul;26(7):1452–1457. [PubMed] [Google Scholar]
  24. Hoshino T., Yamada A., Honda J., Imai Y., Nakao M., Inoue M., Sagawa K., Yokoyama M. M., Oizumi K., Itoh K. Tissue-specific distribution and age-dependent increase of human CD11b+ T cells. J Immunol. 1993 Aug 15;151(4):2237–2246. [PubMed] [Google Scholar]
  25. Kägi D., Ledermann B., Bürki K., Zinkernagel R. M., Hengartner H. Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo. Annu Rev Immunol. 1996;14:207–232. doi: 10.1146/annurev.immunol.14.1.207. [DOI] [PubMed] [Google Scholar]
  26. Labalette M., Leteurtre E., Thumerelle C., Grutzmacher C., Tourvieille B., Dessaint J. P. Peripheral human CD8(+)CD28(+)T lymphocytes give rise to CD28(-)progeny, but IL-4 prevents loss of CD28 expression. Int Immunol. 1999 Aug;11(8):1327–1336. doi: 10.1093/intimm/11.8.1327. [DOI] [PubMed] [Google Scholar]
  27. Lafaille J. J. The role of helper T cell subsets in autoimmune diseases. Cytokine Growth Factor Rev. 1998 Jun;9(2):139–151. doi: 10.1016/s1359-6101(98)00009-4. [DOI] [PubMed] [Google Scholar]
  28. Lehner T. The role of heat shock protein, microbial and autoimmune agents in the aetiology of Behçet's disease. Int Rev Immunol. 1997;14(1):21–32. doi: 10.3109/08830189709116842. [DOI] [PubMed] [Google Scholar]
  29. Linsley P. S., Ledbetter J. A. The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol. 1993;11:191–212. doi: 10.1146/annurev.iy.11.040193.001203. [DOI] [PubMed] [Google Scholar]
  30. Lloyd T. E., Yang L., Tang D. N., Bennett T., Schober W., Lewis D. E. Regulation of CD28 costimulation in human CD8+ T cells. J Immunol. 1997 Feb 15;158(4):1551–1558. [PubMed] [Google Scholar]
  31. Matsui M., Araya S., Wang H-Y, Onai N., Matsushima K., Saida T. Circulating lymphocyte subsets linked to intracellular cytokine profiles in normal humans. Clin Exp Immunol. 2003 Nov;134(2):225–231. doi: 10.1046/j.1365-2249.2003.02291.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mittrücker H. W., Kursar M., Köhler A., Hurwitz R., Kaufmann S. H. Role of CD28 for the generation and expansion of antigen-specific CD8(+) T lymphocytes during infection with Listeria monocytogenes. J Immunol. 2001 Nov 15;167(10):5620–5627. doi: 10.4049/jimmunol.167.10.5620. [DOI] [PubMed] [Google Scholar]
  33. Mollet L., Sadat-Sowti B., Duntze J., Leblond V., Bergeron F., Calvez V., Katlama C., Debré P., Autran B. CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity. Int Immunol. 1998 Mar;10(3):311–323. doi: 10.1093/intimm/10.3.311. [DOI] [PubMed] [Google Scholar]
  34. Monteiro J., Batliwalla F., Ostrer H., Gregersen P. K. Shortened telomeres in clonally expanded CD28-CD8+ T cells imply a replicative history that is distinct from their CD28+CD8+ counterparts. J Immunol. 1996 May 15;156(10):3587–3590. [PubMed] [Google Scholar]
  35. Müller S., Lory J., Corazza N., Griffiths G. M., Z'graggen K., Mazzucchelli L., Kappeler A., Mueller C. Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease. Am J Pathol. 1998 Jan;152(1):261–268. [PMC free article] [PubMed] [Google Scholar]
  36. Nakata M., Kawasaki A., Azuma M., Tsuji K., Matsuda H., Shinkai Y., Yagita H., Okumura K. Expression of perforin and cytolytic potential of human peripheral blood lymphocyte subpopulations. Int Immunol. 1992 Sep;4(9):1049–1054. doi: 10.1093/intimm/4.9.1049. [DOI] [PubMed] [Google Scholar]
  37. Peng S. L., Moslehi J., Robert M. E., Craft J. Perforin protects against autoimmunity in lupus-prone mice. J Immunol. 1998 Jan 15;160(2):652–660. [PubMed] [Google Scholar]
  38. Posnett D. N., Edinger J. W., Manavalan J. S., Irwin C., Marodon G. Differentiation of human CD8 T cells: implications for in vivo persistence of CD8+ CD28- cytotoxic effector clones. Int Immunol. 1999 Feb;11(2):229–241. doi: 10.1093/intimm/11.2.229. [DOI] [PubMed] [Google Scholar]
  39. Raziuddin S., al-Dalaan A., Bahabri S., Siraj A. K., al-Sedairy S. Divergent cytokine production profile in Behçet's disease. Altered Th1/Th2 cell cytokine pattern. J Rheumatol. 1998 Feb;25(2):329–333. [PubMed] [Google Scholar]
  40. Rubesa G., Podack E. R., Sepcić J., Rukavina D. Increased perforin expression in multiple sclerosis patients during exacerbation of disease in peripheral blood lymphocytes. J Neuroimmunol. 1997 Apr;74(1-2):198–204. doi: 10.1016/s0165-5728(96)00236-6. [DOI] [PubMed] [Google Scholar]
  41. Sallusto F., Lenig D., Förster R., Lipp M., Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999 Oct 14;401(6754):708–712. doi: 10.1038/44385. [DOI] [PubMed] [Google Scholar]
  42. Saruhan-Direskeneli Güher, Yentür Sibel P., Akman-Demir Gülşen, Işik Nihal, Serdaroğlu Piraye. Cytokines and chemokines in neuro-Behçet's disease compared to multiple sclerosis and other neurological diseases. J Neuroimmunol. 2003 Dec;145(1-2):127–134. doi: 10.1016/j.jneuroim.2003.08.040. [DOI] [PubMed] [Google Scholar]
  43. Scotet E., Peyrat M. A., Saulquin X., Retiere C., Couedel C., Davodeau F., Dulphy N., Toubert A., Bignon J. D., Lim A. Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes. Eur J Immunol. 1999 Mar;29(3):973–985. doi: 10.1002/(SICI)1521-4141(199903)29:03<973::AID-IMMU973>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
  44. Seko Y., Minota S., Kawasaki A., Shinkai Y., Maeda K., Yagita H., Okumura K., Sato O., Takagi A., Tada Y. Perforin-secreting killer cell infiltration and expression of a 65-kD heat-shock protein in aortic tissue of patients with Takayasu's arteritis. J Clin Invest. 1994 Feb;93(2):750–758. doi: 10.1172/JCI117029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Spaner D., Raju K., Radvanyi L., Lin Y., Miller R. G. A role for perforin in activation-induced cell death. J Immunol. 1998 Mar 15;160(6):2655–2664. [PubMed] [Google Scholar]
  46. Weekes M. P., Wills M. R., Mynard K., Hicks R., Sissons J. G., Carmichael A. J. Large clonal expansions of human virus-specific memory cytotoxic T lymphocytes within the CD57+ CD28- CD8+ T-cell population. Immunology. 1999 Nov;98(3):443–449. doi: 10.1046/j.1365-2567.1999.00901.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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