Low levels of NF-κB/p65 Mark Anergic CD4+ T cells and correlate with disease severity in sarcoidosis

Clinical and Vaccine Immunology

Volumn 18, Issue 2, 2011, Pages 223-234

  Lee, Nam Sihk ^a   Barber, Laura ^a   Kanchwala, Ali ^a   Childs, Carter J H ^a   Kataria, Yash P ^a   Judson, Marc A ^b   Mazer, Mark A ^a   Arce, Sergio ^a  

^a EAST CAROLINA UNIVERSITY   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD3 ANTIGEN; CD3 ZETA ANTIGEN; CD4 ANTIGEN; CD40 LIGAND; CD69 ANTIGEN; GAMMA INTERFERON; I KAPPA B ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 2; PROTEIN KINASE LCK; PROTEIN P105; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR NFATC2; TRANSCRIPTION FACTOR RELA; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CD4+ T LYMPHOCYTE; CLINICAL ARTICLE; CLONAL ANERGY; CONTROLLED STUDY; CYTOKINE PRODUCTION; DISEASE ACTIVITY; DISEASE SEVERITY; EFFECTOR CELL; FEMALE; HUMAN; LYMPHOCYTE ACTIVATION; LYMPHOCYTE PROLIFERATION; MALE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SARCOIDOSIS; SIGNAL TRANSDUCTION;

ADULT; ANTIGENS, CD; ANTIGENS, DIFFERENTIATION, T-LYMPHOCYTE; CD4-POSITIVE T-LYMPHOCYTES; CD40 LIGAND; CELL PROLIFERATION; CLONAL ANERGY; CYTOKINES; GENE EXPRESSION PROFILING; HUMANS; INTERFERON-GAMMA; LECTINS, C-TYPE; MIDDLE AGED; SARCOIDOSIS; SEVERITY OF ILLNESS INDEX; TRANSCRIPTION FACTOR RELA;

EID: 79551488067     PISSN: 15566811     EISSN: 1556679X     Source Type: Journal    
DOI: 10.1128/CVI.00469-10     Document Type: Article

References (75)

1. Aronica, M. A., et al. 1999. Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo. J. Immunol. 163:5116-5124.
2. Auphan, N., J. A. DiDonato, C. Rosette, A. Helmberg, and M. Karin. 1995. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 270:286-290.
3. Baars, P. A., M. M. Maurice, M. Rep, B. Hooibrink, and R. A. van Lier. 1995. Heterogeneity of the circulating human CD4+ T cell population. Further evidence that the CD4+CD45RA-CD27- T cell subset contains specialized primed T cells. J. Immunol. 154:17-25.
4. Baniyash, M. 2004. TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response. Nat. Rev. Immunol. 4:675-687.
5. Barkett, M., and T. D. Gilmore. 1999. Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene 18:6910-6924.
6. Boyum, A. 1968. Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand. J. Clin. Lab. Invest. Suppl. 97:77-89.
7. Breedveld, F. C., and C. L. Verweij. 1997. T cells in rheumatoid arthritis. Br. J. Rheumatol. 36:617-619.
8. Bronstein-Sitton, N., et al. 2003. Sustained exposure to bacterial antigen induces interferon-gamma-dependent T cell receptor zeta down-regulation and impaired T cell function. Nat. Immunol. 4:957-964.
9. Brundula, V., et al. 1999. Diminished levels of T cell receptor zeta chains in peripheral blood T lymphocytes from patients with systemic lupus erythematosus. Arthritis Rheum. 42:1908-1916.
10. Cantrell, D. A. 1996. T cell antigen receptor signal transduction pathways. Cancer Surv. 27:165-175.
11. Chen, E. S., et al. 2008. T cell responses to mycobacterial catalase-peroxidase profile a pathogenic antigen in systemic sarcoidosis. J. Immunol. 181:8784-8796.
12. Chen, L. 2004. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat. Rev. Immunol. 4:336-347.
13. Ciszak, L., E. Pawlak, A. Kosmaczewska, S. Potoczek, and I. Frydecka. 2007. Alterations in the expression of signal-transducing CD3 zeta chain in T cells from patients with chronic inflammatory/autoimmune diseases. Arch. Immunol. Ther. Exp. (Warsz.) 55:373-386.
14. Corn, R. A., et al. 2003. T cell-intrinsic requirement for NF-kappa B induction in postdifferentiation IFN-gamma production and clonal expansion in a Th1 response. J. Immunol. 171:1816-1824.
15. Cox, C. E., A. Davis-Allen, and M. A. Judson. 2005. Sarcoidosis. Med. Clin. North Am. 89:817-828.
16. Daniele, R. P., J. H. Dauber, and M. D. Rossman. 1980. Immunologic abnormalities in sarcoidosis. Ann. Intern. Med. 92:406-416.
17. Day, C. L., et al. 2006. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443:350-354.
18. Fekete, A., et al. 2007. Disturbances in B- and T-cell homeostasis in rheumatoid arthritis: suggested relationships with antigen-driven immune responses. J. Autoimmun. 29:154-163.
19. Fife, B. T., and J. A. Bluestone. 2008. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol. Rev. 224:166-182.
20. Finke, J. H., et al. 1993. Loss of T-cell receptor zeta chain and p56lck in T-cells infiltrating human renal cell carcinoma. Cancer Res. 53:5613-5616.
21. Fontenot, A. P., et al. 2005. Frequency of beryllium-specific, central memory CD4+ T cells in blood determines proliferative response. J. Clin. Invest. 115:2886-2893.
22. Gerondakis, S., R. Grumont, I. Rourke, and M. Grossmann. 1998. The regulation and roles of Rel/NF-kappa B transcription factors during lymphocyte activation. Curr. Opin. Immunol. 10:353-359.
23. + T cells associated with reversible immune dysfunction. J. Virol. 81:9249-9258.
24. Goodwin, J. S., R. DeHoratius, H. Israel, G. T. Peake, and R. P. Messner. 1979. Suppressor cell function in sarcoidosis. Ann. Intern. Med. 90:169-173.
25. Granelli-Piperno, A., and P. Nolan. 1991. Nuclear transcription factors that bind to elements of the IL-2 promoter. Induction requirements in primary human T cells. J. Immunol. 147:2734-2739.
26. Grewal, I. S., and R. A. Flavell. 1998. CD40 and CD154 in cell-mediated immunity. Annu. Rev. Immunol. 16:111-135.
27. Hintzen, R. Q., et al. 1993. Regulation of CD27 expression on subsets of mature T-lymphocytes. J. Immunol. 151:2426-2435.
28. Hudspith, B. N., J. Brostoff, M. W. McNicol, and N. M. Johnson. 1984. Anergy in sarcoidosis: the role of interleukin-1 and prostaglandins in the depressed in vitro lymphocyte response. Clin. Exp. Immunol. 57:324-330.
29. Hughes, C. C., and J. S. Pober. 1996. Transcriptional regulation of the interleukin-2 gene in normal human peripheral blood T cells. Convergence of costimulatory signals and differences from transformed T cells. J. Biol. Chem. 271:5369-5377.
30. Hunninghake, G. W., and R. G. Crystal. 1981. Mechanisms of hypergammaglobulinemia in pulmonary sarcoidosis. Site of increased antibody production and role of T lymphocytes. J. Clin. Invest. 67:86-92.
31. Hunninghake, G. W., and R. G. Crystal. 1981. Pulmonary sarcoidosis: a disorder mediated by excess helper T-lymphocyte activity at sites of disease activity. N. Engl. J. Med. 305:429-434.
32. Iannuzzi, M. C., B. A. Rybicki, and A. S. Teirstein. 2007. Sarcoidosis. N. Engl. J. Med. 357:2153-2165.
33. Isomaki, P., et al. 2001. Prolonged exposure of T cells to TNF downregulates TCR zeta and expression of the TCR/CD3 complex at the cell surface. J. Immunol. 166:5495-5507.
34. Kataria, Y. P., A. L. Sagone, A. G. LoBuglio, and P. A. Bromberg. 1973. In vitro observations on sarcoid lymphocytes and their correlation with cutaneous energy and clinical severity of disease. Am. Rev. Respir. Dis. 108:767-776.
35. Katchar, K., J. Wahlstrom, A. Eklund, and J. Grunewald. 2001. Highly activated T-cell receptor AV2S3(+) CD4(+) lung T-cell expansions in pulmonary sarcoidosis. Am. J. Respir. Crit. Care Med. 163:1540-1545.
36. Kaufmann, D. E., et al. 2007. Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction. Nat. Immunol. 8:1246-1254.
37. Kiani, A., et al. 2004. Expression and regulation of NFAT (nuclear factors of activated T cells) in human CD34+ cells: down-regulation upon myeloid differentiation. J. Leukoc. Biol. 76:1057-1065.
38. Kobayashi, M., et al. 2005. Enhanced expression of programmed death-1 (PD-1)/PD-L1 in salivary glands of patients with Sjogren's syndrome. J. Rheumatol. 32:2156-2163.
39. Kyttaris, V. C., Y. Wang, Y. T. Juang, A. Weinstein, and G. C. Tsokos. 2007. Increased levels of NF-ATc2 differentially regulate CD154 and IL-2 genes in T cells from patients with systemic lupus erythematosus. J. Immunol. 178: 1960-1966.
40. Lai, J. H., et al. 1995. RelA is a potent transcriptional activator of the CD28 response element within the interleukin 2 promoter. Mol. Cell. Biol. 15: 4260-4271.
41. Lougaris, V., R. Badolato, S. Ferrari, and A. Plebani. 2005. Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features. Immunol. Rev. 203:48-66.
42. Lu, L. F., and A. Rudensky. 2009. Molecular orchestration of differentiation and function of regulatory T cells. Genes Dev. 23:1270-1282.
43. Lyons, A. B., and C. R. Parish. 1994. Determination of lymphocyte division by flow cytometry. J. Immunol. Methods 171:131-137.
44. Maggirwar, S. B., E. W. Harhaj, and S. C. Sun. 1997. Regulation of the interleukin-2 CD28-responsive element by NF-ATp and various NF-kappaB/Rel transcription factors. Mol. Cell. Biol. 17:2605-2614.
45. Mandy, F., G. Janossy, M. Bergeron, R. Pilon, and S. Faucher. 2008. Affordable CD4 T-cell enumeration for resource-limited regions: a status report for 2008. Cytometry B Clin. Cytom. 74(Suppl. 1):S27-S39.
46. Mathew, S., K. L. Bauer, A. Fischoeder, N. Bhardwaj, and S. J. Oliver. 2008. The anergic state in sarcoidosis is associated with diminished dendritic cell function. J. Immunol. 181:746-755.
47. Matsuda, M., et al. 1998. Decreased expression of signal-transducing CD3 zeta chains in T cells from the joints and peripheral blood of rheumatoid arthritis patients. Scand. J. Immunol. 47:254-262.
48. Maurice, M. M., et al. 1997. Defective TCR-mediated signaling in synovial T cells in rheumatoid arthritis. J. Immunol. 159:2973-2978.
49. McGuire, K. L., and M. Iacobelli. 1997. Involvement of Rel, Fos, and Jun proteins in binding activity to the IL-2 promoter CD28 response element/AP-1 sequence in human T cells. J. Immunol. 159:1319-1327.
50. Miyara, M., et al. 2006. The immune paradox of sarcoidosis and regulatory T cells. J. Exp. Med. 203:359-370.
51. Moller, D. R. 2003. Treatment of sarcoidosis - from a basic science point of view. J. Intern. Med. 253:31-40.
52. Moller, D. R. 2007. Potential etiologic agents in sarcoidosis. Proc. Am. Thorac. Soc. 4:465-468.
53. Nambiar, M. P., et al. 2001. Dexamethasone modulates TCR zeta chain expression and antigen receptor-mediated early signaling events in human T lymphocytes. Cell. Immunol. 208:62-71.
54. Newman, L. S., et al. 2004. A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am. J. Respir. Crit. Care Med. 170:1324-1330.
55. Otsuji, M., Y. Kimura, T. Aoe, Y. Okamoto, and T. Saito. 1996. Oxidative stress by tumor-derived macrophages suppresses the expression of CD3 zeta chain of T-cell receptor complex and antigen-specific T-cell responses. Proc. Natl. Acad. Sci. U. S. A. 93:13119-13124.
56. Palmer, B. E., et al. 2008. Up-regulation of programmed death-1 expression on beryllium-specific CD4+ T cells in chronic beryllium disease. J. Immunol. 180:2704-2712.
57. Pandiyan, P., et al. 2004. CD152 (CTLA-4) determines the unequal resistance of Th1 and Th2 cells against activation-induced cell death by a mechanism requiring PI3 kinase function. J. Exp. Med. 199:831-842.
58. Parker, D. C. 1993. T cell-dependent B cell activation. Annu. Rev. Immunol. 11:331-360.
59. Paz Morante, M., et al. 2006. Activation-associated phenotype of CD3 T cells in acute graft-versus-host disease. Clin. Exp. Immunol. 145:36-43.
60. Sallusto, F., J. Geginat, and A. Lanzavecchia. 2004. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu. Rev. Immunol. 22:745-763.
61. Scheinman, R. I., P. C. Cogswell, A. K. Lofquist, and A. S. Baldwin, Jr. 1995. Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science 270:283-286.
62. Schubert, L. A., et al. 1995. The human gp39 promoter. Two distinct nuclear factors of activated T cell protein-binding elements contribute independently to transcriptional activation. J. Biol. Chem. 270:29624-29627.
63. Sica, A., et al. 1997. Interaction of NF-kappaB and NFAT with the interferon- gamma promoter. J. Biol. Chem. 272:30412-30420.
64. Smith-Garvin, J. E., G. A. Koretzky, and M. S. Jordan. 2009. T cell activation. Annu. Rev. Immunol. 27:591-619.
65. Sweiss, N. J., et al. 2010. Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations. PLoS. One 5:e9088.
66. Vallabhapurapu, S., and M. Karin. 2009. Regulation and function of NF-kappaB transcription factors in the immune system. Annu. Rev. Immunol. 27:693-733.
67. Van Laethem, F., et al. 2001. Glucocorticoids attenuate T cell receptor signaling. J. Exp. Med. 193:803-814.
68. Wahlstrom, J., et al. 1999. Phenotypic analysis of lymphocytes and monocytes/macrophages in peripheral blood and bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis. Thorax 54:339-346.
69. Weil, R., and A. Israel. 2004. T-cell-receptor- and B-cell-receptor- mediated activation of NF-kappaB in lymphocytes. Curr. Opin. Immunol. 16:374-381.
70. Winterbauer, R. H., and K. G. Kraemer. 1976. The infectious complications of sarcoidosis: a current perspective. Arch. Intern. Med. 136:1356-1362.
71. Wong, H. K., G. M. Kammer, G. Dennis, and G. C. Tsokos. 1999. Abnormal NF-kappa B activity in T lymphocytes from patients with systemic lupus erythematosus is associated with decreased p65-RelA protein expression. J. Immunol. 163:1682-1689.
72. Yamamoto, R., et al. 2008. PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma. Blood 111: 3220-3224.
73. Younes, S. A., et al. 2003. HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity. J. Exp. Med. 198:1909-1922.
74. Zajac, A. J., et al. 1998. Viral immune evasion due to persistence of activated T cells without effector function. J. Exp. Med. 188:2205-2213.
75. Zea, A. H., et al. 1998. Changes in expression of signal transduction proteins in T lymphocytes of patients with leprosy. Infect. Immun. 66:499-504.