Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease

Journal of Clinical Investigation

Volumn 119, Issue 1, 2009, Pages 182-192

  Brochard, Vanessa ^a,b   Combadière, Béhazine ^c   Prigent, Annick ^a,b   Laouar, Yasmina ^d   Perrin, Aline ^a,b   Beray Berthat, Virginie ^a,b   Bonduelle, Olivia ^c   Alvarez Fischer, Daniel ^a,b   Callebert, Jacques ^e   Launay, Jean Marie ^e   Duyckaerts, Charles ^a,b   Flavell, Richard A ^d   Hirsch, Etienne C ^a,b   Hunot, Stéphane ^a,b  

^a PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^b SORBONNE UNIVERSITÉ   (France)

^c INSERM   (France)

^d YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e HÔPITAL LARIBOISIÈRE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; FAS LIGAND; GAMMA INTERFERON; DOPAMINE; FASL PROTEIN, MOUSE; HOMEODOMAIN PROTEIN; RAG 1 PROTEIN; RAG-1 PROTEIN;

AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOPSY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DEATH; CONTROLLED STUDY; DOPAMINERGIC SYSTEM; HUMAN; HUMAN TISSUE; IMMUNE DEFICIENCY; IMMUNE SYSTEM; LYMPHOCYTIC INFILTRATION; MALE; MOUSE; MOUSE STRAIN; NERVE DEGENERATION; NEUROTOXICITY; NONHUMAN; PANCREAS ISLET CELL TUMOR; PARKINSON DISEASE; PRIORITY JOURNAL; SPLEEN CELL; ANIMAL; BRAIN; C57BL MOUSE; CYTOLOGY; DISEASE MODEL; GENETICS; IMMUNOLOGY; METABOLISM; MOUSE MUTANT; NERVE CELL; PARKINSONISM; PATHOLOGY; PHYSIOLOGY;

AGED; AGED, 80 AND OVER; ANIMALS; BRAIN; CD4-POSITIVE T-LYMPHOCYTES; CELL DEATH; DISEASE MODELS, ANIMAL; DOPAMINE; FAS LIGAND PROTEIN; HOMEODOMAIN PROTEINS; HUMANS; IMMUNE SYSTEM; INTERFERON-GAMMA; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; NERVE DEGENERATION; NEURONS; PARKINSON DISEASE; PARKINSONIAN DISORDERS;

EID: 58849107919     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI36470     Document Type: Article

References (56)

1. Dauer, W., and Przedborski, S. 2003. Parkinson's disease: mechanisms and models. Neuron. 39:889-909.
2. Chen, H., et al. 2005. Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann. Neurol. 58:963-967.
3. Wahner, A.D., Bronstein, J.M., Bordelon, Y.M., and Ritz, B. 2007. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology. 69:1836-1842.
4. Nagatsu, T., Mogi, M., Ichinose, H., and Togari, A. 2000. Changes in cytokines and neurotrophins in Parkinson's disease. J. Neural Transm. Suppl. 60:277-290.
5. Czlonkowska, A., Kurkowska-Jastrzebska, I., Czlonkowski, A., Peter, D., and Stefano, G.B. 2002. Immune processes in the pathogenesis of Parkinson's disease - a potential role for microglia and nitric oxide. Med. Sci. Monit. 8:RA165-RA177.
6. Whitton, P.S. 2007. Inflammation as a causative factor in the aetiology of Parkinson's disease. Br. J. Pharmacol. 150:963-976.
7. McGeer, P.L., Itagaki, S., Akiyama, H., and McGeer, E.G. 1988. Rate of cell death in parkinsonism indicates active neuropathological process. Ann. Neurol. 24:574-576.
8. Hunot, S., et al. 1999. FcεRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-α in glial cells. J. Neurosci. 19:3440-3447.
9. Kurkowska-Jastrzebska, I., et al. 1999. The inflammatory reaction following 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine intoxication in mouse. Exp. Neurol. 156:50-61.
10. Janeway, C.A., Jr., and Travers, P. 1997. Immunobiology: the immune system in health and disease. 3rd edition. Garland Publishing Inc. New York, New York, USA. A1-A10.
11. Kortekaas, R., et al. 2005. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann. Neurol. 57:176-179.
12. Engelhardt, B. 2006. Molecular mechanisms involved in T cell migration across the blood-brain barrier. J. Neural Transm. 113:477-485.
13. Serpe, C.J., Kohm, A.P., Huppenbauer, C.B., Sanders, V.M., and Jones, K.J. 1999. Exacerbation of facial motoneuron loss after facial nerve transection in severe combined immunodeficient (scid) mice. J. Neurosci. 19:RC7.
14. Chen, Z., Ljunggren, H.G., Zhu, S.W., Winblad, B., and Zhu, J. 2004. Reduced susceptibility to kainic acid-induced excitotoxicity in T-cell deficient CD4/ CD8(-/-) and middle-aged C57BL/6 mice. J. Neuroimmunol. 146:33-38.
15. Mombaerts, P., et al. 1992. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. Nature. 360:225-231.
16. Fung-Leung, W.P., et al. 1991. CD8 is needed for development of cytotoxic T-cells but not helper T-cells. Cell. 65:443-449.
17. Rahemtulla, A., et al. 1991. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature. 353:180-184.
18. Mount, M.P., et al. 2007. Involvement of interferon-γ in microglial-mediated loss of dopaminergic neurons. J. Neurosci. 27:3328-3337.
19. Takahashi, T., et al. 1994. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell. 76:969-976.
20. Hunot, S., and Hirsch, E.C. 2003. Neuroinflammatory processes in Parkinson's disease. Ann. Neurol. 53(Suppl. 3):S49-S60.
21. Baba, Y., Kuroiwa, A., Uitti, R.G., Wszolek, Z.K., and Yamada, T. 2005. Alterations of T-lymphocyte populations in Parkinson disease. Parkinsonism Relat. Disord. 11:493-498.
22. Cose, S., Brammer, C., Khanna, K.M., Masopust, D., and Lefrançois, L. 2006. Evidence that a significant number of naive T cells enter non-lymphoid organs as part of a normal migratory pathway. Eur. J. Immunol. 36:1423-1433.
23. Togo, T., et al. 2002. Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases. J. Neuroimmunol. 124:83-92.
24. German, D.C., et al. 1996. The neurotoxin MPTP causes degeneration of specific nucleus A8, A9 and A10 dopaminergic neurons in the mouse. Neurodegeneration. 5:299-312.
25. Farkas, E., De Jong, G.I., de Vos, R.A., Jansen Steur, E.N., and Luiten, P.G. 2000. Pathological features of cerebral cortical capillaries are double in Alzheimer's disease and Parkinson's disease. Acta Neuropathol. 100:395-402.
26. Haussermann, P., Kuhn, W., Przuntek, H., and Muller, T. 2001. Integrity of the blood-cerebrospinal fluid barrier in early Parkinson's disease. Neurosci. Lett. 300:182-184.
27. Adams, J.D., Jr., Klaidman, L.K., Odunze, I.N., and Johannenssen, J.N. 1991. Effects of MPTP on the cerebrovasculature. Int. J. Dev. Neurosci. 9:155-159.
28. Zhao, C., Ling, Z., Newman, M.B., Bhatia, A., and Carvey, P.M. 2007. TNF-± knockout and minocycline treatment attenuates blood-brain barrier leakage in MPTP-treated mice. Neurobiol. Dis. 26:36-46.
29. Springer, T.A. 1994. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 76:301-314.
30. Miklossy, J., et al. 2005. Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys. Exp. Neurol. 197:275-283.
31. Jenner, P., and Olanow, C.W. 1998. Understanding cell death in Parkinson's disease. Ann. Neurol. 44(Suppl. 1):S72-S84.
32. Benner, E.J., et al. 2008. Nitrated ±-synuclein immunity accelerates degeneration of nigral dopaminergic neurons. PloS ONE. 3:e1376.
33. Ciesielska, A., et al. 2003. Dynamics of expression of the mRNA for cytokines and inducible nitric synthase in a murine model of the Parkinson's disease. Acta Neurobiol. Exp. (Wars.) 63:117-126.
34. Hayley, S., et al. 2004. Regulation of dopaminergic loss by Fas in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. J. Neurosci. 24:2045-2053.
35. Landau, A.M., et al. 2005. Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease. J. Exp. Med. 202:575-581.
36. Ashany, D., et al. 1995. Th1 CD4+ lymphocytes delete activated macrophages through the Fas/ APO-1 antigen pathway. Proc. Natl. Acad. Sci. U. S. A. 92:11225-11229.
37. Park, D.R., et al. 2003. Fas (CD95) induces proinf lammatory cytokine responses by human monocytes and monocyte-derived macrophages. J. Immunol. 170:6209-6216.
38. Choi, C., and Benveniste, E.N. 2004. Fas ligand/ fas system in the brain: regulator of immune and apoptosis responses. Brain Res. Rev. 44:65-81.
39. Ferrer, I., Blanco, R., Cutillas, B., and Ambrosio, S. 2000. Fas and Fas-L expression in Huntington's disease and Parkinson's disease. Neuropathol. Appl. Neurobiol. 26:424-433.
40. Giuliani, F., Goodyer, C.G., Antel, J.P., and Yong, V.W. 2003. Vulnerability of human neurons to T cell-mediated cytotoxicity. J. Immunol. 171:368-379.
41. Ju, S.T., Cui, H., Panka, D.J., Ettinger, R., and Marshak-Rothstein, A. 1994. Participation of target Fas protein in apoptosis pathway induced by CD4+ Th1 and CD8+ cytotoxic T cells. Proc. Natl. Acad. Sci. U. S. A. 91:4185-4189.
42. Rousselet, E., et al. 2002. Role of TNF-alpha receptors in mice intoxicated with the parkinsonian toxin MPTP. Exp. Neurol. 177:183-192.
43. Ferger, B., Leng, A., Mura, A., Hengerer, B., and Feldon, J. 2004. Genetic ablation of tumor necrosis factor-alpha (TNF-alpha) and pharmacological inhibition of TNF-synthesis attenuates MPTP toxicity in mouse striatum. J. Neurochem. 89:822-833.
44. Sriram, K., Miller, D.B., and O'Callaghan, J.P. 2006. Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-alpha. J. Neurochem. 96:706-718.
45. Zhu, J., and Paul, W.E. 2008. CD4 T cells: fates, functions, and faults. Blood. 112:1557-1568.
46. Kebir, H., et al. 2007. Human Th17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat. Med. 13:1173-1175.
47. Beers, D.R., Henkel, J.S., Zhao, W., Wang, J., and Appel, S.H. 2008. 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. 105:15558-15563.
48. Banerjee, R., et al. 2008. Adaptive immune neuroprotection in G93A-SOD1 amyotrophic lateral sclerosis mice. PLoS ONE. 3:e2740.
49. Benner, E.J., et al. 2004. Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease. Proc. Natl. Acad. Sci. U. S. A. 101:9435-9440.
50. Reynolds, A.D., et al. 2007. Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease. J. Leukoc. Biol. 82:1083-1094.
51. Luster, A.D., Alon, R., and von Andrian, U.H. 2005. Immune cell migration in inflammation: present and future therapeutic targets. Nat. Immunol. 6:1182-1190.
52. Braak, H., and Del Tredici, K. 2008. Assessing fetal nerve cell grafts in Parkinson's disease. Nat. Med. 14:483-485.
53. Welte, T., et al. 2003. STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: A critical role of STAT3 in innate immunity. Proc. Natl. Acad. Sci. U. S. A. 100:1879-1884.
54. Hunot, S., et al. 2004. JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease. Proc. Natl. Acad. Sci. U. S. A. 101:665-670.
55. Hunot, S., et al. 1997. Nuclear translocation of NFkappaB is increased in dopaminergic neurons of patients with Parkinson disease. Proc. Natl. Acad. Sci. U. S. A. 94:7531-7536.
56. Liberatore, G.T., et al. 1999. Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat. Med. 5:1403-1409.