Increased T-cell reactivity and elevated levels of CD8+ memory T-cells in Alzheimer's disease-patients and T-cell hyporeactivity in an Alzheimer's disease-mouse model: Implications for immunotherapy

NeuroMolecular Medicine

Volumn 9, Issue 4, 2007, Pages 340-354

  Schindowski, Katharina ^a,b   Eckert, Anne ^a,c   Peters, Jürgen ^a   Gorriz, Corinna ^a   Schramm, Uta ^a   Weinandi, Thomas ^a   Maurer, Konrad ^a   Frölich, Lutz ^a,d   Müller, Walter E ^a  

^a GOETHE UNIVERSITY   (Germany)

^b UNIV LILLE   (France)

^c UNIVERSITY OF BASEL   (Switzerland)

^d UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

4G10; Activation induced cell death (AICD); Apoliporotein E (ApoE); BrdU; CD3; CD69; Hyposensitive; Neural immune interaction; Neurodegeneration; Neuroinflammation

Indexed keywords

APOLIPOPROTEIN E; PHOSPHOTYROSINE;

AGED; ALZHEIMER DISEASE; ANIMAL; ARTICLE; BLOOD; CD4 CD8 RATIO; CD8+ T LYMPHOCYTE; DISEASE MODEL; FEMALE; FLOW CYTOMETRY; GENETICS; HUMAN; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; IMMUNOTHERAPY; LYMPHOCYTE COUNT; MALE; METABOLISM; METHODOLOGY; MONONUCLEAR CELL; MOUSE; PHYSIOLOGY; TRANSGENIC MOUSE;

AGED; ALZHEIMER DISEASE; ANIMALS; APOLIPOPROTEINS E; CD4-CD8 RATIO; CD8-POSITIVE T-LYMPHOCYTES; DISEASE MODELS, ANIMAL; FEMALE; FLOW CYTOMETRY; HUMANS; IMMUNOLOGIC MEMORY; IMMUNOTHERAPY; LEUKOCYTES, MONONUCLEAR; LYMPHOCYTE COUNT; MALE; MICE; MICE, TRANSGENIC; PHOSPHOTYROSINE;

EID: 38749120306     PISSN: 15351084     EISSN: 15591174     Source Type: Journal    
DOI: 10.1007/s12017-007-8015-9     Document Type: Article

References (103)

1. Adunsky, A., Baram, D., Hershkowitz, M., & Mekori, Y. A. (1991). Increased cytosolic free calcium in lymphocytes of Alzheimer patients. Journal of Neuroimmunology, 33, 167-172.
2. Adunsky, A., Diver-Haber, A., Becker, D., & Hershkowitz, M. (1995). Basal and activated intracellular calcium ion concentrations in mononuclear cells of Alzheimer's disease and unipolar depression. The Journals of Gerontology. Series A Biological Sciences and Medical Sciences, 50, B201-B204.
3. Aloisi, F., Ria, F., Columba-Cabezas, S., Hess, H., Penna, G., & Adorini, L. (1999). Relative efficiency of microglia, astrocytes, dendritic cells and B cells in naive CD4+ T cell priming and Th1/Th2 cell restimulation. European Journal of Immunology, 29, 2705-2714. (Pubitemid 30098995)
4. Blanchard, V., Moussaoui, S., Czech, C., Touchet, N., Bonici, B., Planche, M., Canton, T., Jedidi, I., Gohin, M., Wirths, O., Bayer, T. A., Langui, D., Duyckaerts, C., Tremp, G., & Pradier, L. (2003). Time sequence of maturation of dystrophic neurites associated with Abeta deposits in APP/PS1 transgenic mice. Experimental Neurology, 184, 247-263. (Pubitemid 37444035)
5. Bongioanni, P., Boccardi, B., Borgna, M., Castagna, M., & Mondino, C. (1997a). T-cell interferon gamma binding in patients with dementia of the Alzheimer type. Archives of Neurology, 54, 457-462. (Pubitemid 27172866)
6. Bongioanni, P., Boccardi, B., Borgna, M., & Rossi, B. (1998). T-lymphocyte interleukin 6 receptor binding in patients with dementia of Alzheimer type. Archives of Neurology, 55, 1305-1308. (Pubitemid 28465862)
7. Bongioanni, P., Romano, M. R., Sposito, R., Castagna, M., Boccardi, B., & Borgna, M. (1997b). T-cell tumour necrosis factor-alpha receptor binding in demented patients. Journal of Neurology, 244, 418-425. (Pubitemid 27379647)
8. Carson, M. J., Reilly, C. R., Sutcliffe, J. G., & Lo, D. (1999). Disproportionate recruitment of CD8+ T cells into the central nervous system by professional antigen-presenting cells. American Journal of Pathology, 154, 481-494. (Pubitemid 29094098)
9. Carson, M. J., & Sutcliffe, J. G. (1999). Balancing function vs. self defense: The CNS as an active regulator of immune responses. Journal of Neuroscience Research, 55, 1-8.
10. Chandok, M. R., & Farber, D. L. (2004). Signaling control of memory T cell generation and function. Seminars in Immunology, 16, 285-293. (Pubitemid 39446556)
11. Chiodetti, L., Choi, S., Barber, D. L., & Schwartz, R. H. (2006). Adaptive tolerance and clonal anergy are distinct biochemical states. Journal of Immunology, 176, 2279-2291. (Pubitemid 43201675)
12. Cho, B. K., Wang, C., Sugawa, S., Eisen, H. N., & Chen, J. (1999). Functional differences between memory and naive CD8 T cells. Proceedings of the National Academy of Sciences of the United States of America, 96, 2976-2981. (Pubitemid 29148829)
13. Colton, C. A., Brown, C. M., & Vitek, M. P. (2005). Sex steroids, APOE genotype and the innate immune system. Neurobiology of Aging, 26, 363-372. (Pubitemid 40082720)
14. Cornet, A., Bettelli, E., Oukka, M., Cambouris, C., Avellana-Adalid, V., Kosmatopoulos, K., & Liblau, R. S. (2000). Role of astrocytes in antigen presentation and naive T-cell activation. Journal of Neuroimmunology, 106, 69-77. (Pubitemid 30256079)
15. Cribbs, D. H., Ghochikyan, A., Vasilevko, V., Tran, M., Petrushina, I., Sadzikava, N., Babikyan, D., Kesslak, P., Kieber-Emmons, T., Cotman, C. W., & Agadjanyan, M. G. (2003). Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid. International Immunology, 15, 505-514. (Pubitemid 36432403)
16. Czech, C., Delaere, P., Macq, A. F., Reibaud, M., Dreisler, S., Touchet, N., Schombert, B., Mazadier, M., Mercken, L., Theisen, M., Pradier, L., Octave, J. N., Beyreuther, K., & Tremp, G. (1997). Proteolytical processing of mutated human amyloid precursor protein in transgenic mice. Brain Research. Molecular Brain Research, 47, 108-116. (Pubitemid 27284484)
17. Dai, Z., Nasr, I. W., Reel, M., Deng, S., Diggs, L., Larsen, C. P., Rothstein, D. M., & Lakkis, F. G. (2005). Impaired recall of CD8 memory T cells in immunologically privileged tissue. Journal of Immunology, 174, 1165-1170.
18. Das, P., Murphy, M. P., Younkin, L. H., Younkin, S. G., & Golde, T. E. (2001). Reduced effectiveness of Abeta1-42 immunization in APP transgenic mice with significant amyloid deposition. Neurobiology of Aging, 22, 721-727. (Pubitemid 33055611)
19. DeSilva, D. R., Feeser, W. S., Tancula, E. J., & Scherle, P. A. (1996). Anergic T cells are defective in both jun NH2-terminal kinase and mitogen-activated protein kinase signaling pathways. The Journal of Experimental Medicine, 183, 2017-2023. (Pubitemid 26158894)
20. DeSilva, D. R., Jones, E. A., Feeser, W. S., Manos, E. J., & Scherle, P. A. (1997). The p38 mitogen-activated protein kinase pathway in activated and anergic Th1 cells. Cellular Immunology, 180, 116-123. (Pubitemid 27459745)
21. Dorszewska, J., Florczak, J., Rozycka, A., Jaroszewska-Kolecka, J., Trzeciak, W. H., & Kozubski, W. (2005). Polymorphisms of the CHRNA4 gene encoding the alpha4 subunit of nicotinic acetylcholine receptor as related to the oxidative DNA damage and the level of apoptotic proteins in lymphocytes of the patients with Alzheimer's disease. DNA and Cell Biology, 24, 786-794. (Pubitemid 41832102)
22. Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C. M., Perez-tur, J., Hutton, M., Buee, L., Harigaya, Y., Yager, D., Morgan, D., Gordon, M. N., Holcomb, L., Refolo, L., Zenk, B., Hardy, J., & Younkin, S. (1996). Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature, 383, 710-713. (Pubitemid 26360645)
23. Ebstein, R. P., Nemanov, L., Lubarski, G., Dano, M., Trevis, T., & Korczyn, A. D. (1996). Changes in expression of lymphocyte amyloid precursor protein mRNA isoforms in normal aging and Alzheimer's disease. Brain Research. Molecular Brain Research, 35, 260-268. (Pubitemid 26036754)
24. Eckert, A., Forstl, H., Hartmann, H., Czech, C., Monning, U., Beyreuther, K., & Muller, W. E. (1995). The amplifying effect of beta-amyloid on cellular calcium signalling is reduced in Alzheimer's disease. Neuroreport, 6, 1199-1202.
25. Eckert, A., Oster, M., Zerfass, R., Hennerici, M., & Muller, W. E. (2001a). Elevated levels of fragmented DNA nucleosomes in native and activated lymphocytes indicate an enhanced sensitivity to apoptosis in sporadic Alzheimer's disease. Specific differences to vascular dementia. Dementia and Geriatric Cognitive Disorders, 12, 98-105. (Pubitemid 32149714)
26. Eckert, A., Schindowski, K., Leutner, S., Luckhaus, C., Touchet, N., Czech, C., & Muller, W. E. (2001b). Alzheimer's disease-like alterations in peripheral cells from presenilin-1 transgenic mice. Neurobiology of Disease, 8, 331-342. (Pubitemid 32382486)
27. Eisenbraun, M. D., Tamir, A., & Miller, R. A. (2000). Altered composition of the immunological synapse in an anergic, age-dependent memory T cell subset. Journal of Immunology, 164, 6105-6112. (Pubitemid 30408786)
28. Engelhardt, B., & Ransohoff, R. M. (2005). The ins and outs of T-lymphocyte trafficking to the CNS: Anatomical sites and molecular mechanisms. Trends in Immunology, 26, 485-495. (Pubitemid 41139258)
29. Esplugues, E., Sancho, D., Vega-Ramos, J., Martinez, C., Syrbe, U., Hamann, A., Engel, P., Sanchez-Madrid, F., & Lauzurica, P. (2003). Enhanced antitumor immunity in mice deficient in CD69. The Journal of Experimental Medicine, 197, 1093-1106. (Pubitemid 36570065)
30. Fiala, M., Liu, Q. N., Sayre, J., Pop, V., Brahmandam, V., Graves, M. C., & Vinters, H. V. (2002). Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier. European Journal of Clinical Investigation, 32, 360-371. (Pubitemid 36228397)
31. + T cells. Science, 271, 1276-1278.
32. Ford, A. L., Foulcher, E., Lemckert, F. A., & Sedgwick, J. D. (1996). Microglia induce CD4 T lymphocyte final effector function and death. The Journal of Experimental Medicine, 184, 1737-1745. (Pubitemid 26404465)
33. Frey, C., Bonert, A., Kratzsch, T., Rexroth, G., Rosch, W., Muller-Spahn, F., Maurer, K., Muller, W. E., & Eckert, A. (2006). Apolipoprotein E epsilon 4 is associated with an increased vulnerability to cell death in Alzheimer's disease. Journal of Neural Transmission.
34. Furlan, R., Brambilla, E., Sanvito, F., Roccatagliata, L., Olivieri, S., Bergami, A., Pluchino, S., Uccelli, A., Comi, G., & Martino, G. (2003). Vaccination with amyloid-beta peptide induces autoimmune encephalomyelitis in C57/BL6 mice. Brain, 126, 285-291. (Pubitemid 36172736)
35. Galimberti, D., Schoonenboom, N., Scheltens, P., Fenoglio, C., Venturelli, E., Pijnenburg, Y. A., Bresolin, N., & Scarpini, E. (2006). Intrathecal chemokine levels in Alzheimer disease and frontotemporal lobar degeneration. Neurology, 66, 146-147. (Pubitemid 43739618)
36. Gee, J. R., & Keller, J. N. (2005). Astrocytes: Regulation of brain homeostasis via apolipoprotein E. The International Journal of Biochemistry and Cell Biology, 37, 1145-1150. (Pubitemid 40381190)
37. + memory T-cell subsets in response to antigen or homeostatic cytokines. Blood, 101, 4260-4266.
38. Gilman, S., Koller, M., Black, R. S., Jenkins, L., Griffith, S. G., Fox, N. C., Eisner, L., Kirby, L., Rovira, M. B., Forette, F., & Orgogozo, J. M. (2005). Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology, 64, 1553-1562. (Pubitemid 40617691)
39. Giuliani, F., Goodyer, C. G., Antel, J. P., & Yong, V. W. (2003). Vulnerability of human neurons to T cell-mediated cytotoxicity. Journal of Immunology, 171, 368-379. (Pubitemid 36745310)
40. + lymphocytes in Alzheimer's disease and in older persons with Down's syndrome. Neurobiology of Aging, 14, 177-185.
41. Guidi, L., Tricerri, A., Frasca, D., Vangeli, M., Errani, A. R., & Bartoloni, C. (1998). Psychoneuroimmunology and aging. Gerontology, 44, 247-261. (Pubitemid 28403385)
42. Hanisch, U. K., Neuhaus, J., Quirion, R., & Kettenmann, H. (1996). Neurotoxicity induced by interleukin-2: Involvement of infiltrating immune cells. Synapse, 24, 104-114.
43. + T-cells. Glia, 22, 348-359.
44. Hubert, P., Grenot, P., Autran, B., & Debre, P. (1997). Analysis by flow cytometry of tyrosine-phosphorylated proteins in activated T-cell subsets on whole blood samples. Cytometry, 29, 83-91.
45. Iarlori, C., Gambi, D., Gambi, F., Lucci, I., Feliciani, C., Salvatore, M., & Reale, M. (2005). Expression and production of two selected beta-chemokines in peripheral blood mononuclear cells from patients with Alzheimer's disease. Experimental Gerontology, 40, 605-611. (Pubitemid 41074807)
46. + homeostasis in lymphoblasts from patients with late-onset Alzheimer disease. Alzheimer Disease and Associated Disorders, 11, 220-227.
47. Ikeda, T., Yamamoto, K., Takahashi, K., Kaneyuki, H., & Yamada, M. (1991a). Interleukin-2 receptor in peripheral blood lymphocytes of Alzheimer's disease patients. Acta Psychiatrica Scandinavica, 84, 262-265.
48. Ikeda, T., Yamamoto, K., Takahashi, K., & Yamada, M. (1991b). Immune system-associated antigens on the surface of peripheral blood lymphocytes in patients with Alzheimer's disease. Acta Psychiatrica Scandinavica, 83, 444-448.
49. Itagaki, S., McGeer, P. L., & Akiyama, H. (1988). Presence of T-cytotoxic suppressor and leucocyte common antigen positive cells in Alzheimer's disease brain tissue. Neuroscience Letters, 91, 259-264.
50. Jang, I. K., & Gu, H. (2003). Negative regulation of TCR signaling and T-cell activation by selective protein degradation. Current Opinion in Immunology, 15, 315-320.
51. Lassmann, H., & Ransohoff, R. M. (2004). The CD4-Th1 model for multiple sclerosis: A critical [correction of crucial] re-appraisal. Trends in Immunology, 25, 132-137. (Pubitemid 38249486)
52. Ledoux, S., Rebai, N., Dagenais, A., Shaw, I. T., Nalbantoglu, J., Sekaly, R. P., & Cashman, N. R. (1993). Amyloid precursor protein in peripheral mononuclear cells is up-regulated with cell activation. Journal of Immunology, 150, 5566-5575. (Pubitemid 23180671)
53. Lemere, C. A., Maron, R., Selkoe, D. J., & Weiner, H. L. (2001). Nasal vaccination with beta-amyloid peptide for the treatment of Alzheimer's disease. DNA and Cell Biology, 20, 705-711. (Pubitemid 34072837)
54. Lemere, C. A., Maron, R., Spooner, E. T., Grenfell, T. J., Mori, C., Desai, R., Hancock, W. W., Weiner, H. L., & Selkoe, D. J. (2000). Nasal A beta treatment induces anti-A beta antibody production and decreases cerebral amyloid burden in PD-APP mice. Annals of the New York Academy of Sciences, 920, 328-331. (Pubitemid 32056589)
55. Leutner, S., Czech, C., Schindowski, K., Touchet, N., Eckert, A., & Muller, W. E. (2000). Reduced antioxidant enzyme activity in brains of mice transgenic for human presenilin-1 with single or multiple mutations. Neuroscience Letters, 292, 87-90.
56. Ligthart, G. J., Corberand, J. X., Fournier, C., Galanaud, P., Hijmans, W., Kennes, B., Muller-Hermelink, H. K., & Steinmann, G. G. (1984). Admission criteria for immunogerontological studies in man: The SENIEUR protocol. Mechanisms of Ageing and Development, 28, 47-55. (Pubitemid 15222465)
57. Lombardi, V. R., Garcia, M., Rey, L., & Cacabelos, R. (1999). Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer's Disease (AD) individuals. Journal of Neuroimmunology, 97, 163-171. (Pubitemid 29301426)
58. Maesaka, J. K., Palaia, T., Chowdhury, S. A., Shimamura, T., Fishbane, S., Reichman, W., Coyne, A., O'Rear, J. J., & El-Sabban, M. E. (1999). Partial characterization of apoptotic factor in Alzheimer plasma. The American Journal of Physiology, 276, F521-527. (Pubitemid 29217381)
59. Masliah, E., Hansen, L., Adame, A., Crews, L., Bard, F., Lee, C., Seubert, P., Games, D., Kirby, L., & Schenk, D. (2005). Abeta vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease. Neurology, 64, 129-131. (Pubitemid 40082949)
60. Matyszak, M. K., Denis-Donini, S., Citterio, S., Longhi, R., Granucci, F., & Ricciardi-Castagnoli, P. (1999). Microglia induce myelin basic protein-specific T cell anergy or T cell activation, according to their state of activation. European Journal of Immunology, 29, 3063-3076.
61. McGeer, P. L., Akiyama, H., Itagaki, S., & McGeer, E. G. (1989). Immune system response in Alzheimer's disease. The Canadian Journal of Neurological Sciences, 16, 516-527. (Pubitemid 19278363)
62. Mirshahidi, S., Ferris, L. C., & Sadegh-Nasseri, S. (2004). The magnitude of TCR engagement is a critical predictor of T cell anergy or activation. Journal of Immunology, 172, 5346-5355. (Pubitemid 38542033)
63. Mirshahidi, S., Huang, C. T., & Sadegh-Nasseri, S. (2001). Anergy in peripheral memory CD4(+) T cells induced by low avidity engagement of T cell receptor. The Journal of Experimental Medicine, 194, 719-731. (Pubitemid 32983009)
64. Monning, U., Konig, G., Banati, R. B., Mechler, H., Czech, C., Gehrmann, J., Schreiter-Gasser, U., Masters, C. L., & Beyreuther, K. (1992). Alzheimer beta A4-amyloid protein precursor in immunocompetent cells. The Journal of Biological Chemistry, 267, 23950-23956. (Pubitemid 23088209)
65. Monsonego, A., Maron, R., Zota, V., Selkoe, D. J., & Weiner, H. L. (2001). Immune hyporesponsiveness to amyloid beta-peptide in amyloid precursor protein transgenic mice: Implications for the pathogenesis and treatment of Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 98, 10273-10278. (Pubitemid 32803010)
66. Monsonego, A., Zota, V., Karni, A., Krieger, J. I., Bar-Or, A., Bitan, G., Budson, A. E., Sperling, R., Selkoe, D. J., & Weiner, H. L. (2003). Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. The Journal of Clinical Investigation, 112, 415-422. (Pubitemid 38063770)
67. Orgogozo, J. M., Gilman, S., Dartigues, J. F., Laurent, B., Puel, M., Kirby, L. C., Jouanny, P., Dubois, B., Eisner, L., Flitman, S., Michel, B. F., Boada, M., Frank, A., & Hock, C. (2003). Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology, 61, 46-54. (Pubitemid 36818745)
68. Palotas, A., Kalman, J., Palotas, M., Juhasz, A., Janka, Z., & Penke, B. (2002). Beta-amyloid-induced increase in the resting intracellular calcium concentration gives support to tell Alzheimer lymphocytes from control ones. Brain Research Bulletin, 58, 203-205. (Pubitemid 34753091)
69. Panossian, L. A., Porter, V. R., Valenzuela, H. F., Zhu, X., Reback, E., Masterman, D., Cummings, J. L., & Effros, R. B. (2003). Telomere shortening in T cells correlates with Alzheimer's disease status. Neurobiology of Aging, 24, 77-84. (Pubitemid 35454145)
70. Park, E., Alberti, J., Mehta, P., Dalton, A., Sersen, E., & Schuller-Levis, G. (2000). Partial impairment of immune functions in peripheral blood leukocytes from aged men with Down's syndrome. Clinical Immunology, 95, 62-69. (Pubitemid 30202818)
71. Pirttila, T., Mattinen, S., & Frey, H. (1992). The decrease of CD8-positive lymphocytes in Alzheimer's disease. Journal of Neurological Sciences, 107, 160-165.
72. Ratts, R. B., Karandikar, N. J., Hussain, R. Z., Choy, J., Northrop, S. C., Lovett-Racke, A. E., & Racke, M. K. (2006). Phenotypic characterization of autoreactive T cells in multiple sclerosis. Journal of Neuroimmunology, 178, 100-110. (Pubitemid 44354819)
73. Robinson Agramonte, M., Dorta-Contreras, A. J., & Lorigados Pedre, L. (2001). Immune events in central nervous system of early and late onset Alzheimer's disease patients. Revista de Neurologia, 32, 901-904.
74. Rogers, J., & Mufson, E. J. (1990). Demonstrating immune-related antigens in Alzheimer's disease brain tissue. Neurobiology of Aging, 11, 477-479. (Pubitemid 20274581)
75. Rota, E., Bellone, G., Rocca, P., Bergamasco, B., Emanuelli, G., & Ferrero, P. (2006). Increased intrathecal TGF-beta1, but not IL-12, IFN-gamma and IL-10 levels in Alzheimer's disease patients. Neurological Sciences, 27, 33-39. (Pubitemid 44026855)
76. Rubin, B., Llobera, R., Gouaillard, C., Alcover, A., & Arnaud, J. (2000). Dissection of the role of CD3gamma chains in profound but reversible T-cell receptor down-regulation. Scandinavian Journal of Immunology, 52, 173-183.
77. Sala, G., Galimberti, G., Canevari, C., Raggi, M. E., Isella, V., Facheris, M., Appollonio, I., & Ferrarese, C. (2003). Peripheral cytokine release in Alzheimer patients: Correlation with disease severity. Neurobiology of Aging, 24, 909-914. (Pubitemid 36962975)
78. Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Liao, Z., Lieberburg, I., Motter, R., Mutter, L., Soriano, F., Shopp, G., Vasquez, N., Vandevert, C., Walker, S., Wogulis, M., Yednock, T., Games, D., & Seubert, P. (1999). Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature, 400, 173-177. (Pubitemid 29327547)
79. Schindowski, K., Frohlich, L., Maurer, K., Muller, W. E., & Eckert, A. (2002). Age-related impairment of human T lymphocytes' activation: Specific differences between CD4(+) and CD8(+) subsets. Mechanisms of Ageing and Development, 123, 375-390. (Pubitemid 34024925)
80. Schindowski, K., Kratzsch, T., Peters, J., Steiner, B., Leutner, S., Touchet, N., Maurer, K., Czech, C., Pradier, L., Frolich, L., Muller, W. E., & Eckert, A. (2003). Impact of aging: Sporadic, and genetic risk factors on vulnerability to apoptosis in Alzheimer's disease. Neuromolecular Medicine, 4, 161-178.
81. Schindowski, K., Leutner, S., Muller, W. E., & Eckert, A. (2000). Age-related changes of apoptotic cell death in human lymphocytes. Neurobiology of Aging, 21, 661-670.
82. + T and natural killer cells in Alzheimer's disease. Pharmacopsychiatry, 39, 220-228.
83. + memory and virgin T cells. European Journal of Immunology, 20, 1957-1963.
84. Schmid, I., Uittenbogaart, C. H., Keld, B., & Giorgi, J. V. (1994). A rapid method for measuring apoptosis and dual-color immunofluorescence by single laser flow cytometry. Journal of Immunological Methods, 170, 145-157. (Pubitemid 24122504)
85. Schuessel, K., Schafer, S., Bayer, T. A., Czech, C., Pradier, L., Muller-Spahn, F., Muller, W. E., & Eckert, A. (2005). Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice. Neurobiology of Disease, 18, 89-99. (Pubitemid 40092899)
86. Seabrook, T. J., Thomas, K., Jiang, L., Bloom, J., Spooner, E., Maier, M., Bitan, G., & Lemere, C. A. (2007). Dendrimeric Abeta1-15 is an effective immunogen in wildtype and APP-tg mice. Neurobiology of Aging, 28, 813-823. (Pubitemid 46589741)
87. + T cell responses in the central nervous system. Journal of Experimental Medicine, 173, 1235-1246.
88. Shalit, F., Sredni, B., Brodie, C., Kott, E., & Huberman, M. (1995). T lymphocyte subpopulations and activation markers correlate with severity of Alzheimer's disease. Clinical Immunology and Immunopathology, 75, 246-250.
89. Singh, V. K. (1990). Neuroimmune axis as a basis of therapy in Alzheimer's disease. Progress in Drug Research, 34, 383-393.
90. Stieler, J. T., Lederer, C., Bruckner, M. K., Wolf, H., Holzer, M., Gertz, H. J., & Arendt, T. (2001). Impairment of mitogenic activation of peripheral blood lymphocytes in Alzheimer's disease. Neuroreport, 12, 3969-3972. (Pubitemid 33152435)
91. + T cells as a potential diagnostic marker of Alzheimer's disease. Journal of Neuroimmunology, 132, 164-172.
92. Tanchot, C., Rosado, M. M., Agenes, F., Freitas, A. A., & Rocha, B. (1997). Lymphocyte homeostasis. Seminars in Immunology, 9, 331-337. (Pubitemid 28021490)
93. Togo, T., Akiyama, H., Iseki, E., Kondo, H., Ikeda, K., Kato, M., Oda, T., Tsuchiya, K., & Kosaka, K. (2002). Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases. Journal of Neuroimmunology, 124, 83-92. (Pubitemid 34212013)
94. Torres, P. S., Alcover, A., Zapata, D. A., Arnaud, J., Pacheco, A., Martin-Fernandez, J. M., Villasevil, E. M., Sanal, O., & Regueiro, J. R. (2003). TCR dynamics in human mature T lymphocytes lacking CD3 gamma. Journal of Immunology, 170, 5947-5955. (Pubitemid 36682574)
95. Town, T., Tan, J., Flavell, R. A., & Mullan, M. (2005). T-cells in Alzheimer's disease. Neuromolecular Medicine, 7, 255-264. (Pubitemid 41507148)
96. Town, T., Tan, J., Sansone, N., Obregon, D., Klein, T., & Mullan, M. (2001). Characterization of murine immunoglobulin G antibodies against human amyloid-beta1-42. Neuroscience Letters, 307, 101-104. (Pubitemid 32568384)
97. Town, T., Vendrame, M., Patel, A., Poetter, D., DelleDonne, A., Mori, T., Smeed, R., Crawford, F., Klein, T., Tan, J., & Mullan, M. (2002). Reduced Th1 and enhanced Th2 immunity after immunization with Alzheimer's beta-amyloid(1-42). Journal of Neuroimmunology, 132, 49-59. (Pubitemid 35333325)
98. Trieb, K., Ransmayr, G., Sgonc, R., Lassmann, H., & Grubeck-Loebenstein, B. (1996). APP peptides stimulate lymphocyte proliferation in normals, but not in patients with Alzheimer's disease. Neurobiology of Aging, 17, 541-547. (Pubitemid 26274253)
99. Valitutti, S., Muller, S., Cella, M., Padovan, E., & Lanzavecchia, A. (1995). Serial triggering of many T-cell receptors by a few peptide-MHC complexes. Nature, 375, 148-151.
100. Vingtdeux, V., Hamdane, M., Gompel, M., Begard, S., Drobecq, H., Ghestem, A., Grosjean, M. E., Kostanjevecki, V., Grognet, P., Vanmechelen, E., Buee, L., Delacourte, A., & Sergeant, N. (2005). Phosphorylation of amyloid precursor carboxy-terminal fragments enhances their processing by a gamma-secretase-dependent mechanism. Neurobiology of Disease, 20, 625-637. (Pubitemid 41476288)
101. Weishaupt, A., Jander, S., Bruck, W., Kuhlmann, T., Stienekemeier, M., Hartung, T., Toyka, K. V., Stoll, G., & Gold, R. (2000). Molecular mechanisms of high-dose antigen therapy in experimental autoimmune encephalomyelitis: Rapid induction of Th1-type cytokines and inducible nitric oxide synthase. Journal of Immunology, 165, 7157-7163. (Pubitemid 32001192)
102. Wenham, P. R., Price, W. H., & Blandell, G. (1991). Apolipoprotein E genotyping by one-stage PCR. Lancet, 337, 1158-1159.
103. Zhang, J., Kong, Q., Zhang, Z., Ge, P., Ba, D., & He, W. (2003). Telomere dysfunction of lymphocytes in patients with Alzheimer disease. Cognitive and Behavirol Neurology, 16, 170-176. (Pubitemid 37243440)