Regulatory T cells in CNS injury: The simple, the complex and the confused

Trends in Molecular Medicine

Volumn 17, Issue 10, 2011, Pages 541-547

  Walsh, James T ^a   Kipnis, Jonathan ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD25 ANTIBODY; CD4 ANTIGEN; CD8 ANTIGEN; CELL ANTIBODY; INTERLEUKIN 17; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 22; INTERLEUKIN 6; MYELIN BASIC PROTEIN; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; TOLL LIKE RECEPTOR 2; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; ALZHEIMER DISEASE; ANTIGEN PRESENTING CELL; AUTOIMMUNITY; BLAST INJURY; BLOOD BRAIN BARRIER; CD25+ T LYMPHOCYTE; CD4+ CD25+ T LYMPHOCYTE; CELL DAMAGE; CELL SURVIVAL; CENTRAL NERVOUS SYSTEM; CONFUSION; EFFECTOR CELL; IMMUNE RESPONSE; IMMUNE SYSTEM; INNATE IMMUNITY; LYMPHOCYTE PROLIFERATION; MAJOR HISTOCOMPATIBILITY COMPLEX; NERVE DEGENERATION; NERVE FIBER GROWTH; NERVE REGENERATION; NERVOUS SYSTEM INJURY; NEUROPROTECTION; NONHUMAN; OPTIC NERVE INJURY; PARKINSON DISEASE; REGULATORY T LYMPHOCYTE; REVIEW; SPINAL CORD INJURY; SPLEEN CELL; STROKE; T LYMPHOCYTE ACTIVATION;

ANIMALS; AUTOIMMUNITY; CENTRAL NERVOUS SYSTEM; HUMANS; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; T-LYMPHOCYTES, REGULATORY;

EID: 80053574871     PISSN: 14714914     EISSN: 1471499X     Source Type: Journal    
DOI: 10.1016/j.molmed.2011.05.012     Document Type: Review

References (71)

1. Mizell M. Limb regeneration: induction in the newborn opossum. Science 1968, 161:283-286.
2. Yoles E., Schwartz M. Degeneration of spared axons following partial white matter lesion: implications for optic nerve neuropathies. Exp. Neurol. 1998, 153:1-7.
3. Bramlett H.M., Dietrich W.D. Pathophysiology of cerebral ischemia and brain trauma: similarities and differences. J. Cereb. Blood Flow Metab. 2004, 24:133-150.
4. Thuret S., et al. Therapeutic interventions after spinal cord injury. Nat. Rev. Neurosci. 2006, 7:628-643.
5. Anderson M.J., Waxman S.G. Caudal spinal cord of the teleost Sternarchus albifrons resembles regenerating cord. Anat. Rec. 1983, 205:85-92.
6. Walder S., et al. Up-regulation of neural stem cell markers suggests the occurrence of dedifferentiation in regenerating spinal cord. Dev. Genes Evol. 2003, 213:625-630.
7. Chen M.S., et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 2000, 403:434-439.
8. Rolls A., et al. Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Med. 2008, 5:e171.
9. Tanaka E.M., Ferretti P. Considering the evolution of regeneration in the central nervous system. Nat. Rev. Neurosci. 2009, 10:713-723.
10. Barker C.F., Billingham R.E. Immunologically privileged sites. Adv. Immunol. 1977, 25:1-54.
11. Hickey W.F., et al. T-lymphocyte entry into the central nervous system. J. Neurosci. Res. 1991, 28:254-260.
12. Abbott N.J., et al. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 2006, 7:41-53.
13. Lee S.C., et al. Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta. J. Immunol. 1993, 150:2659-2667.
14. Sawada M., et al. Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Res. 1989, 491:394-397.
15. Wong D., Dorovini-Zis K. Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in primary cultures of human brain microvessel endothelial cells by cytokines and lipopolysaccharide. J. Neuroimmunol. 1992, 39:11-21.
16. Lassmann H., et al. Microglial cells are a component of the perivascular glia limitans. J. Neurosci. Res. 1991, 28:236-243.
17. Guth L., et al. The unique histopathological responses of the injured spinal cord. Implications for neuroprotective therapy. Ann. N. Y. Acad. Sci. 1999, 890:366-384.
18. Popovich P.G., et al. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J. Comp. Neurol. 1997, 377:443-464.
19. Klein L., et al. Antigen presentation in the thymus for positive selection and central tolerance induction. Nat. Rev. Immunol. 2009, 9:833-844.
20. Benichou G., et al. Immunogenicity and tolerogenicity of self-major histocompatibility complex peptides. J. Exp. Med. 1990, 172:1341-1346.
21. Fontenot J.D., et al. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 2003, 4:330-336.
22. Setoguchi R., et al. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J. Exp. Med. 2005, 201:723-735.
23. Sakaguchi S., et al. Regulatory T cells and immune tolerance. Cell 2008, 133:775-787.
24. Thornton A.M., Shevach E.M. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 1998, 188:287-296.
25. Vignali D.A.A., et al. How regulatory T cells work. Nat. Rev. Immunol. 2008, 8:523-532.
26. Curotto de Lafaille M.A., Lafaille J.J. Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor?. Immunity 2009, 30:626-635.
27. Stockinger B., et al. Th17 T cells: linking innate and adaptive immunity. Semin. Immunol. 2007, 19:353-361.
28. Kohm A.P., et al. Cutting edge: anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells. J. Immunol. 2006, 176:3301-3305.
29. Kubo T., et al. Regulatory T cell suppression and anergy are differentially regulated by proinflammatory cytokines produced by TLR-activated dendritic cells. J. Immunol. 2004, 173:7249-7258.
30. Valencia X., et al. TNF downmodulates the function of human CD4+CD25hi T-regulatory cells. Blood 2006, 108:253-261.
31. Piao J., et al. Enhancement of T-cell-mediated anti-tumour immunity via the ectopically expressed glucocorticoid-induced tumour necrosis factor receptor-related receptor ligand (GITRL) on tumours. Immunology 2009, 127:489-499.
32. Yu S., et al. B cell-deficient NOD.H-2h4 mice have CD4+CD25+ T regulatory cells that inhibit the development of spontaneous autoimmune thyroiditis. J. Exp. Med. 2006, 203:349-358.
33. Pace L., et al. Cutting edge: IL-4-induced protection of CD4+CD25- Th cells from CD4+CD25+ regulatory T cell-mediated suppression. J. Immunol. 2006, 176:3900-3904.
34. Sutmuller R.P., et al. Toll-like receptor 2 controls expansion and function of regulatory T cells. J. Clin. Invest. 2006, 116:485-494.
35. Johnson T.V., et al. Bacterial DNA confers neuroprotection after optic nerve injury by suppressing CD4+CD25+ regulatory T-cell activity. Invest. Ophthalmol. Vis. Sci. 2007, 48:3441-3449.
36. Kipnis J., et al. Dopamine, through the extracellular signal-regulated kinase pathway, downregulates CD4+CD25+ regulatory T-cell activity: implications for neurodegeneration. J. Neurosci. 2004, 24:6133-6143.
37. Mazzanti B., et al. T-cell response to myelin basic protein and lipid-bound myelin basic protein in patients with multiple sclerosis and healthy donors. J. Neuroimmunol. 1998, 82:96-100.
38. Finn O.J. Molecular origins of cancer - cancer immunology. N. Engl. J. Med. 2008, 358:2704-2715.
39. Moalem G., et al. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat. Med. 1999, 5:49-55.
40. Fisher J., et al. Vaccination for neuroprotection in the mouse optic nerve: implications for optic neuropathies. J. Neurosci. 2001, 21:136-142.
41. Beers D.R., et al. CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:15558-15563.
42. Kipnis J., et al. Neuroprotective autoimmunity: naturally occurring CD4(+)CD25(+) regulatory T cells suppress the ability to withstand injury to the central nervous system. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:15620-15625.
43. Kipnis J., et al. Myelin specific Th1 cells are necessary for post-traumatic protective autoimmunity. J. Neuroimmunol. 2002, 130:78-85.
44. Wolf S.A., et al. Neuroprotection by T-cells depends on their subtype and activation state. J. Neuroimmunol. 2002, 133:72-80.
45. O'Connor R.A., Anderton S.M. Foxp(3+) regulatory T cells in the control of experimental CNS autoimmune disease. J. Neuroimmunol. 2008, 193:1-11.
46. Zhang H., et al. TGF-beta-induced myelin peptide-specific regulatory T cells mediate antigen-specific suppression of induction of experimental autoimmune encephalomyelitis. J. Immunol. 2010, 184:6629-6636.
47. Caspi R. Autoimmunity in the immune privileged eye: pathogenic and regulatory T cells. Immunol. Res. 2008, 42:41-50.
48. McMahon E.J., et al. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat. Med. 2005, 11:335-339.
49. Cabbage S.E., et al. Regulatory T cells maintain long-term tolerance to myelin basic protein by inducing a novel, dynamic state of T cell tolerance. J. Immunol. 2007, 178:887-896.
50. Reddy J., et al. Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:15434-15439.
51. Kipnis J., et al. Low-dose gamma-irradiation promotes survival of injured neurons in the central nervous system via homeostasis-driven proliferation of T cells. Eur. J. Neurosci. 2004, 19:1191-1198.
52. Schwartz M., Kipnis J. Autoimmunity on alert: naturally occurring regulatory CD4(+)CD25(+) T cells as part of the evolutionary compromise between a 'need' and a 'risk'. Trends Immunol. 2002, 23:530-534.
53. Kipnis J., et al. Dual effect of CD4(+)CD25(+) regulatory T cells in neurodegeneration: a dialogue with microglia. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:14663-14669.
54. Gavin M.A., et al. Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat. Immunol. 2002, 3:33-41.
55. Setiady Y.Y., et al. In vivo depletion of CD4+FOXP3+ Treg cells by the PC61 anti-CD25 monoclonal antibody is mediated by FcgammaRIII+ phagocytes. Eur. J. Immunol. 2010, 40:780-786.
56. Liesz A., et al. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat. Med. 2009, 15:192-199.
57. Lahl K., et al. Selective depletion of Foxp3(+) regulatory T cells induces a scurfy-like disease. J. Exp. Med. 2007, 204:57-63.
58. Ren X., et al. CD4(+)FoxP3(+) regulatory T-cells in cerebral ischemic stroke. Metab. Brain Dis. 2011, 26:87-90.
59. Tenorio E.P., et al. Depletion with PC61 mAb before Toxoplasma gondii infection eliminates mainly Tregs in BALB/c mice but activated cells in C57BL/6J mice. FEMS Immunol. Med. Microbiol. 2011, 10.1111/j.1574-695X.2011.00805.x.
60. Rich R.R., Pierce C.W. Biological expressions of lymphocyte activation. II. Generation of a population of thymus-derived suppressor lymphocytes. J. Exp. Med. 1973, 137:649-659.
61. Bennett C.L., et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 2001, 27:20-21.
62. Sakaguchi S., et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995, 155:1151-1164.
63. Huang X.Y., et al. CD 4+T cells in the pathobiology of neurodegenerative disorders. J. Neuroimmunol. 2009, 211:3-15.
64. Liu Y.W., et al. Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE. Nat. Med. 2006, 12:518-525.
65. Schwartz M. Optic nerve crush: protection and regeneration. Brain Res. Bull. 2004, 62:467-471.
66. Bradbury E.J., McMahon S.B. Spinal cord repair strategies: why do they work?. Nat. Rev. Neurosci. 2006, 7:644-653.
67. Springer J.E., et al. Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury. Nat. Med. 1999, 5:943-946.
68. Lo E.H., et al. Mechanisms, challenges and opportunities in stroke. Nat. Rev. Neurosci. 2003, 4:399-415.
69. Tu W., et al. DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage in stroke. Cell 2010, 140:222-234.
70. Abrahamson E.E., et al. Caspase inhibition therapy abolishes brain trauma-induced increases in Abeta peptide: implications for clinical outcome. Exp. Neurol. 2006, 197:437-450.
71. DeKosky S.T., et al. Traumatic brain injury - football, warfare, long-term effects. N. Engl. J. Med. 2010, 363:1293-1296.