Hostname: page-component-77c89778f8-vsgnj Total loading time: 0 Render date: 2024-07-17T08:15:13.393Z Has data issue: false hasContentIssue false
  • English
  • Français

Immunological and histochemical analyses of cerebrospinal fluid and peripheral blood from patients with neurological and psychiatric disorders

Published online by Cambridge University Press:  24 June 2014

Horst-G. Maxeiner ,
Markus Thomas Rojewski ,
Hayrettin Tumani ,
Sibylle Herzog ,
Dietmar Fuchs ,
Anita Schmitt ,
Michael Schmitt  and
Karl Bechter
Horst-G. Maxeiner
Affiliation:
Clinic for Psychiatry and Psychotherapy II, Guenzburg, Department of Psychiatry II, Ulm University, Germany
Markus Thomas Rojewski
Affiliation:
Institute for Transfusion Medicine, Ulm University and Institute for Clinical Transfusion Medicine and Immunogenetics Ulm gGmbH, Germany
Hayrettin Tumani
Affiliation:
Department of Neurology, Ulm University, Germany
Sibylle Herzog
Affiliation:
Institute of Virology, Justus-Liebig-University Giessen, Germany
Dietmar Fuchs
Affiliation:
Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria
Anita Schmitt
Affiliation:
Institute for Transfusion Medicine, Ulm University and Institute for Clinical Transfusion Medicine and Immunogenetics Ulm gGmbH, Germany
Michael Schmitt
Affiliation:
Department of Internal Medicine III, Ulm University, Germany
Karl Bechter
Affiliation:
Clinic for Psychiatry and Psychotherapy II, Guenzburg, Department of Psychiatry II, Ulm University, Germany
Get access Rights & Permissions [Opens in a new window]

Abstract:

Epidemiological, clinical and post mortem studies indicate that inflammatory and immune reactions are involved in the pathomechanisms of affective and schizophrenic spectrum disorders. However, in psychiatric patients, only sporadic investigation on immunochemistry has been performed and information about immunofunction derived by investigation of immunocompetent cells in the CSF is not available to date.

Here we present an interdisciplinary work of neurologists, psychiatrists and hemato-immunologists focusing on the immunology of psychiatric and neurological disorders. In a first study including 63 patients with therapy resistant affective and schizophrenic spectrum disorders we applied conventional, validated neurological CSF investigation such as analysis of albumin, IgG, IgA, IgM, oligoclonal IgG and specific antibodies, cell count and interpreted the data by Reibergrams.

In a second study, we applied the highly sensitive and specific multicolour flowcytometry of paired samples of CSF and peripheral blood cells to characterize the immunostatus of psychiatric and neurological patients. We demonstrate that flowcytometry technology constitutes an appropriate method to investigate subsets of lymphocytes even with low CSF cell numbers, and therefore as a promising diagnostic tool for routine purposes in the differential diagnosis of psychiatric diseases. Furthermore, knowledge of the frequencies of T cell subsets such as the T regulatory cell type might open new avenues to models of psychiatric and neurological diseases as well as diagnostic and monitoring implications.

Keywords

Cerebrospinal fluid – affective disorders – schizophrenic disorders – low level CNS inflammation – Blood-CSF barrier function- T-cell, Flow Cytometry
Type
Psychoimmunology Symposium: The Impact of Dysfunctional Endocrine and Immune Systems on Psychiatric Disorders
Information
Acta Neuropsychiatrica , Volume 21 , Issue S2: Special Issue: Abstracts of 49th Neuropsychiatric Pula Congress, 17-20 June 2009, Pula, Croatia , June 2009 , pp. 51 - 57
Copyright
Copyright © 2009 John Wiley & Sons A/S

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References:

1.Davis, KL, Stewert, DG, Friedman, JI, Buchsbaum, M, Harvey, PD, Hof, PRet al.White matter changes in schizophrenia: evidence for myelin-related dysfunction. Arch Gen Psychiatry 2003;60:443–456.CrossRefGoogle ScholarPubMed
2.Sperner-Unterweger, B. Immunological aetiology of major psychiatric disorders: evidence and therapeutic implications. Drugs 2005;65:1493–1520.CrossRefGoogle ScholarPubMed
3.Irwin, MR, Miller, AH.Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun 2007;21:374–383.CrossRefGoogle ScholarPubMed
4.Yolken, RH, Torrey, EF.Are some cases of psychosis caused by microbial agents? A review of the evidence. Mol Psychiatry 2008;13:470–479CrossRefGoogle ScholarPubMed
5.Licinio, J, Wong, ML.The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection. Mol Psychiatry 1999;4:317–327CrossRefGoogle ScholarPubMed
6.Meyer, U, Nyffeler, M, Schwendener, S, Knuesel, I, Yee, BK, Feldon, J.Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after In Utero immune challenge. Neuropsychopharmacology 2008;33:441–456.CrossRefGoogle ScholarPubMed
7.Buka, SL, Cannon, TD, Torrey, EF, Yolken, RH; Collaborative Study Group on the Perinatal Origins of Severe Psychiatric Disorders. Maternal exposure to herpes simplex virus and risk of psychosis among adult offspring. Biol Psychiatry 2008;63:809–815.CrossRefGoogle Scholar
8.Dalman, C, Allebeck, P, Gunnell, D, Harrison, G, Kristensson, K, Lewis, Get al.Infections in the CNS during childhood and the risk of subsequent psychotic illness: a cohort study ofmore than one million Swedish subjects. Am J Psychiatry 2008;165:59–65.CrossRefGoogle Scholar
9.Bechter, K, Bogerts, B.Abstracts of the 9th Psychoimmunology Expert Meeting: Neuropsychoimmunology of Psychoses. Immune and inflammatory aspects of psychoses. In Vivo 2007,21:917–953.Google Scholar
10.Rioux, JD, Abbas, AK.Paths to understanding the genetic basis of autoimmune disease. Nature 2005;435:584–589.CrossRefGoogle ScholarPubMed
11.Dickerson, FB, Boronow, JJ, Stallings, CR, Origoni, AE, Yolken, RH.Reduction of symptoms by valacyclovir in cytomegalo-virus-seropositive individuals with schizophrenia. Am J Psychiatry 2003;160:2234–2236.CrossRefGoogle ScholarPubMed
12.Torrey, EF, Leweke, MF, Schwarz, MJ, Mueller, N, Bachmann, S, Schroeder, J, Dickerson, F, Yolken, RH.Cytomegalovirus and schizophrenia. CNS Drugs 2006;20(11):879–85.CrossRefGoogle ScholarPubMed
13.Bechter, K. Infektionen und Depression – Allgemeine Aspekte und spezifische Ausloser. Neurotransmitter 2008;1:46–50.Google Scholar
14.Torrey, EF, Yolken, RH.Toxoplasma gondii and schizophrenia. Emerg Infect Dis 2003;9(11):1375–1380.CrossRefGoogle ScholarPubMed
15.Eaton, WW, Byrne, M, Ewald, H, Mors, O, Chen, CY, Agerbo, E, Mortensen, PB.Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry 2006;163:521–528.CrossRefGoogle ScholarPubMed
16.Müller, N, Riedel, M, Scheppach, C, Brandstätter, B, Sokullu, S, Krampe, Ket al.Beneficial antipsychotic effect of celecoxib add-on therapy compared to risperidone alone in schizophrenia. Am J Psychiatry 2002;159:1029–1034.CrossRefGoogle ScholarPubMed
17.Müller, N, Schwarz, MJ, Dehning, S, Douhe, A, Cerovecki, A, Goldstein-Müller, Bet al.The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 2006;11:680–684.CrossRefGoogle ScholarPubMed
18.Müller, N, Strassnig, M, Schwarz, MJ, Ulmschneider, M, Riedel, M.COX-2 inhibitors as adjunctive therapy in schizophrenia. Expert Opin Investig Drugs 2004;13(8):1033–1044.CrossRefGoogle ScholarPubMed
19.Bechter, K, Herzog, S, Schreiner, V, Brinkmeier, H, Aulkemeyer, P, Weber, Fet al.Borna disease virus-related therapy-resistant depression improved after cerebrospinal fluid filtration. J Psychiatric Res 2000;34:393–396.CrossRefGoogle ScholarPubMed
20.Bechter, K, Schreiner, V, Herzog, S, Breitinger, N, Wollinsky, KH, Brinkmeier, H, Aulkemeyer, P, Weber, F, Schüttler, R. Liquorfiltration als experimentelle Therapie bei therapieresist-enten Psychosen Borna Disease Virus-seropositiver Patienten: Therapeutische Effekte, Befunde. Psychiat Prax 2003;30(Suppl. 2):S216–S220Google Scholar
21.Ehrenreich, H, Hinze-Selch, D, Stawicki, S, Aust, C, Knolle-Veentjer, S, Wilms, Set al.Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin. Mol Psychiatry 2007;12:206–220.CrossRefGoogle ScholarPubMed
22.Knight, JG, Menkes, DB, Highton, J, Adams, DD.Rationale for a trial of immunosuppressive therapy in acute schizophrenia. Mol Psychiatry 2007;12:424–431.CrossRefGoogle ScholarPubMed
23.Smith, RS.A comprehensive macrophage-T-lymphocyte theory of schizophrenia. Med Hypotheses 1992;39:248–257.CrossRefGoogle ScholarPubMed
24.Myint, AM, Kim, YK.Cytokine-serotonin interactions through indoleamine 2,3-dioxygenase: a neurodegenerative hypothesis of depression. Med Hypotheses 2003;61:519–525.CrossRefGoogle ScholarPubMed
25.Leonard, B. Inflammation, depression and dementia: Are they connected? Neurochem Res 2007;32:1749–1756.CrossRefGoogle ScholarPubMed
26.Müller, N, Schwarz, MJ.The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression. Mol Psychiatry 2007;12:988–1000.CrossRefGoogle ScholarPubMed
27.Bechter, K. Mild encephalitis underlying psychiatric disorder –A reconsideration and hypothesis exemplified on Borna disease. Neurol Psychiatry Brain Res 2001;9:55–70.Google Scholar
28.Wildemann, B, Oschmann, P, Reiber, H (eds.): Neurologische Labordiagnostik, Thieme, Stuttgart, 2006.CrossRefGoogle Scholar
29.Sindic, CJ, M-P, Van Antwerpen. Goffette, S. The intrathecal humoral immune response: laboratory analysis and clinical relevance. Clin Chem Lab Med 2001;39:333–340.CrossRefGoogle ScholarPubMed
30.Reiber, H, Peter, JB.Cerebrospinal fluid analysis – disease-related data patterns and evaluation programs. J Neurol Sci 2001;184:101–122.CrossRefGoogle ScholarPubMed
31.Dotevall, L, Fuchs, D, Reibnegger, G, Wachter, H, Hagberg, L.Cerebrospinal fluid and serum neopterin levels in patients with Lyme neuroborreliosis. Infection 1990;18:210–214.CrossRefGoogle ScholarPubMed
32.Heyes, MP, Brew, BJ, Saito, K, Quearry, BJ, Price, RW, Lee, Ket al.Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and beta 2-microglobulin in cerebro-spinal fluid and serum of HIV-1-infected patients. J Neuroim-munol 1992;40:71–80.CrossRefGoogle ScholarPubMed
33.Hagberg, L, Dotevall, L, Norkrans, G, Larsson, M, Wachter, H, Fuchs, D.Cerebrospinal fluid neopterin concentrations in central nervous system infection. J Infect Dis 1993;168:1285–1288.CrossRefGoogle ScholarPubMed
34.Wurster, U. Elektrophereseverfahren-Nachweis und Bedeutung von oligoklonalen Banden. In: Zettl, U., Lehmitz, R., Mix, E. (eds) Klinische Labordiagnostik. Walther de Gruyter: Berlin, 2005, pp. 208–238.Google Scholar
35.Bechter, K, Bindl, A, Horn, M, Schreiner, V.A case of therapy resistant depression with fatigue - seemingly strep-tococcal associated autoimmune disorder. Nervenarzt 2007;78:338–341.CrossRefGoogle Scholar
36.Bloch, KC, Glaser, C.Diagnostic approaches for patients with suspected encephalitis. Curr Infect Dis Rep 2007;9:315–322.CrossRefGoogle ScholarPubMed
37.Rose, NR.Predictive autoantibodies: Past, present and future. In: Conrad, K., Chan, E., Fritzler, M.J., Sack, U., Shoenfeld, Y., Wilks, A.S. (eds) From etiopathogensis to the prediction of autoimmune diseases: Relevance of autoantibodies. Report on the 8th Dresden Symposium on Autoantibodies. Autoantigens, Autoantibodies, Autoimmunity. Papst Lengerich 2007; Vol. 5, pp 6–15.Google Scholar
38.Harel, M, Shoenfeld, Y.Predicting and presenting autoimmunity, myth or reality? Ann NY Acad Sci 2006;1069:322–334.CrossRefGoogle ScholarPubMed
39.Cherner, M, Cysique, L, Heaton, RK, Marcotte, TD, Ellis, RJ, Masliah, Eet al.Neuropathologic confirmation of definitional criteria for human immunodeficiency virus-associated neuro-cognitive disorders. J Neurovirol 2007;13:23–28.CrossRefGoogle Scholar
40.Uranova, N, Orlovskaya, D, Vikhreva, O, Zimina, I, Kolomeets, N, Vostrikov, V, Rachmanova, V.Electron microscopy of olgiodendroglia in severe mental illness. Brain Res Bull 2001;55:597–610.CrossRefGoogle ScholarPubMed
41.Uranova, N, Vostrikov, V, Orlovskaya, D, Rachmanova, V.Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophr Res 2004;67:269–275.CrossRefGoogle ScholarPubMed
42.Steiner, J, Bielau, H, Bernstein, HG, Bogerts, B, Wunderlich, MT.Increased cerebrospinal fluid and serum levels of S100B in first-onset schizophrenia are not related to a degenerative release of glial fibrillar acidic protein, myelin basic protein and neurone-specific enolase from glia or neurones. J Neurol Neurosurg Psychiatry 2006;77:1284–1287.CrossRefGoogle ScholarPubMed
43.Steiner, J, Bielau, H, Brisch, R, Danos, P, Ullrich, O, Mawrin, Cet al.Immunological aspects in the neurobiology of suicide: Elevated microglial density in schizophrenia and depression is associated with suicide. J Psychiatric Res 2008;42:151–157.CrossRefGoogle ScholarPubMed
44.Hanson, DR, Gottesman, II.Theories of schizophrenia: a genetic-inflammatory-vascular synthesis. BMC Med Genet 2005;6:7.CrossRefGoogle ScholarPubMed
45.Wong, ML, Dong, C, Maestre-Mesa, J, Licinio, J.Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response. Mol Psychiatry 2008;13:800–812.CrossRefGoogle ScholarPubMed
46.Maxeiner, HG, Rojewski, MT, Schmitt, A, Tumani, H, Bechter, K, Schmitt, M.Flow cytometric analysis of T cell subsets in paired samples of cerebrospinal fluid and peripheral blood from patients with neurological and psychiatric disorders. Brain Behav Immun 2008.Google Scholar
47.Oleszak, EL, Zhang, X, Lin, WL, Lu, S, Chang, JR, Tsygankov, Aet al.Immunopathology ofmultiple sclerosis and psychoses. In Vivo 2007;21:945–946.Google Scholar
48.Reiber, H, Peter, JB.Cerebrospinal fluid analysis – disease-related data patterns and evaluation programs. J Neurol Sci 2001;184:101–122.CrossRefGoogle ScholarPubMed
49.Nikkilä, HV, Müller, K, Ahokas, A, Miettinen, K, Rimón, R, Andersson, LC.Accumulation of macrophages in the CSF of schizophrenic patients during acute psychotic episodes. Am J Psychiatry 1999;156:1725–1729.CrossRefGoogle ScholarPubMed
50.Oleszak, EL, Lin, WL, Chang, JR, Herzog, S, Bechter, K.Clonally expanded T cells are present in the CSF of patients with major depression. World J. Biol Psychiatry 2001;2:60S.Google Scholar
51.Oleszak, EL, Lin, WL, Chang, JR, Zhang, X, Herzog, S, Bhattacharjee, M, Rudner, G, Platsoucas, CD, Bechter, K.T cells in the CSF of patients with major depression are clonally expanded. Am Psychiat Assoc, Ann Meeting Philadelphia 18.05.-23.05. 2002, New Res Abstr 2002, NR 352.Google Scholar
52.Atanackovic, D, Kroger, H, Serke, S, Deter, HC.Immune parameters in patients with anxiety or depression during psychotherapy. J Affect Disord 2004;81(3):201–209.CrossRefGoogle ScholarPubMed
53.Boscarino, JA, Chang, J: Higher abnormal leukocyte and lymphocyte counts 20 years after exposure to severe stress: research and clinical implications. Psychosom Med 1999;61(3):378–386.CrossRefGoogle ScholarPubMed
54.Cazzullo, CL, Saresella, M, Roda, K, Calvo, MG, Bertrando, P, Doria, S, Clerici, M, Salvaggio, A, Ferrante, P.Increased levels of CD8+ and CD4+ 45RA+ lymphocytes in schizophrenic patients. Schizophr Res 1998;31(1):49–55.CrossRefGoogle ScholarPubMed
55.Ye, Z, Huang, H, Hao, S, Xu, S, Yu, H, Van Den Hurk, S, Xiang, J. IL-10 has a distinct immunoregulatory effect on naive and active T cell subsets. J Interferon Cytokine Res 2007;27(12):1031–1038.CrossRefGoogle Scholar
56.McDyer, JF, Li, Z, John, S, Yu, X, Wu, CY, Ragheb, JA.IL-2 receptor blockade inhibits late, but not early, IFN-gamma and CD40 ligand expression in human T cells: disruption of both IL-12-dependent and -independent pathways of IFN-gamma production. J Immunol 2002;169(5):2736–2746.CrossRefGoogle ScholarPubMed
57.Walker, LS.CD4+ CD25+ Treg: divide and rule? Immunology 2004;111(2):129–37.CrossRefGoogle ScholarPubMed
58.Maes, M, Bosmans, E, Suy, E, Vandervorst, C, De Jonckheere, C, Raus, J.Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology 1990-1991;24(3):115–120.CrossRefGoogle ScholarPubMed
59.Morris, JC, Waldmann, TAAdvances in interleukin 2 receptor targeted treatment. Ann Rheum Dis 200;59 (Suppl 1):i109–i114.CrossRefGoogle Scholar
60.Baecher-Allan, C, Hafler, DA.Human regulatory T cells and their role in autoimmune disease. Immunol Rev 2006;212:203–216.CrossRefGoogle ScholarPubMed
61.Lindsey, WB, Lowdell, MW, Marti, GE, Abbasi, F, Zenger, V, King, KM, Lamb, LS Jr.CD69 expression as an index of T-cell function: assay standardization, validation and use in monitoring immune recovery. Cytotherapy 2007;9(2):123–132.CrossRefGoogle ScholarPubMed
62.Sancho, D, Gomez, M, Sanchez-Madrid, F. CD69 is an immunoregulatory molecule induced following activation. Trends Immunol 2005;26(3):136–140.CrossRefGoogle ScholarPubMed
63.Mihaylova, I, Deruyter, M, Rummens, JL, Bosmans, E, Maes, M.Decreased expression of CD69 in chronic fatigue syndrome in relation to inflammatory markers: evidence for a severe disorder in the early activation of T lymphocytes and natural killer cells. Neuro Endocrinol Lett 2007;28(4).Google ScholarPubMed
64.Kosmaczewska, A, Bilinska, M, Ciszak, L, Noga, L, Pawlak, E, Szteblich, A, Podemski, R, Frydecka, I.Different patterns of activation markers expression and CD4+ T-cell responses to ex vivo stimulation in patients with clinically quiescent multiple sclerosis (MS). J Neuroimmunol 2007.CrossRefGoogle ScholarPubMed
65.Perrella, O, Carrieri, PB, De Mercato, R, Buscaino, GAMarkers of activated T lymphocytes and T cell receptor gamma/delta + in patients with multiple sclerosis. Eur Neurol 1993;33(2):152–155.CrossRefGoogle Scholar
66.Feger, U, Luther, C, Poeschel, S, Melms, A, Tolosa, E, Wiendl, H.Increased frequency of CD4+ CD25+ regulatory T cells in the cerebrospinal fluid but not in the blood of multiple sclerosis patients. Clin Exp Immunol 2007;147(3):412–418.CrossRefGoogle Scholar
67.Tchilian, EZ, Beverley, PC.Altered CD45 expression and disease. Trends Immunol 2006;27(3):146–153.CrossRefGoogle ScholarPubMed
68.Holms, N. CD45: All is not yet crystal clear. Immunology 2005;117:145–155.CrossRefGoogle Scholar
69.Okuda, Y, Okuda, M, Apatoff, BR, Posnett, DN.The activation of memory CD4(+) T cells and CD8(+) T cells in patients with multiple sclerosis. J Neurol Sci 2005;235(1-2):11–17.CrossRefGoogle ScholarPubMed
70.Craddock, RM, Lockstone, HE, Rider, DA, Wayland, MT, Harris, LJ, McKenna, PJ, Bahn, S.Altered T-cell function in schizophrenia: a cellular model to investigate molecular disease mechanisms. PLoS ONE 2007;2:e692.CrossRefGoogle ScholarPubMed
71.Atanackovic, D, Kröger, H, Serke, S, Deter, HC.Immune parameters in patients with anxiety or depression during psychotherapy. J Affect Disord 2004;81(3):201–209.CrossRefGoogle ScholarPubMed
72.Boscarino, JA, Chang, J.Higher abnormal leukocyte and lymphocyte counts 20 years after exposure to severe stress: research and clinical implications. Psychosom Med 1999;61(3):378–386.CrossRefGoogle ScholarPubMed
73.Cosentino, M, Fietta, A, Caldiroli, E, Marino, F, Rispoli, L, Comelli, M, Lecchini, S, Frigo, G.Assessment of lymphocyte subsets and neutrophil leukocyte function in chronic psychiatric patients on long-term drug therapy. Prog Neuropsychopharmacol Biol Psychiatry 1996;20(7):1117–1129.CrossRefGoogle ScholarPubMed
74.Cazzullo, CL, Saresella, M, Roda, K, Calvo, MG, Bertrando, P, Doria, S, Clerici, M, Salvaggio, A, Ferrante, P.Increased levels of CD8+ and CD4+ 45RA+ lymphocytes in schizophrenic patients. Schizophr Res 1998;31(1):49–55.CrossRefGoogle ScholarPubMed
75.Pollmacher, T, Haack, M, Schuld, A, Reichenberg, A, Yirmiya, R.Low levels of circulating inflammatory cytokines-do they affect human brain functions? Brain Behav Immun 2002;16(5):525–532.CrossRefGoogle ScholarPubMed
76.Kronfol, Z, Remick, DG.Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry 2000;157(5):683–694.CrossRefGoogle ScholarPubMed
77.Schiepers, OJ, Wichers, MC, Maes, M. Cytokines and major depression. 2005;29(2):201–217.Google ScholarPubMed
78.McDyer, JF, Li, Z, John, S, Yu, X, Wu, CY, Ragheb, JA.IL-2 receptor blockade inhibits late, but not early, IFN-gamma and CD40 ligand expression in human T cells: disruption of both IL-12-dependent and -independent pathways of IFN-gamma production. J Immunol 20021;169(5):2736–2746.CrossRefGoogle ScholarPubMed
79.Maes, M, Bosmans, E, Suy, E, Vandervorst, C, De Jonckheere, C, Raus, J.Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsy-chobiology 1990–1991;24(3):115–120.CrossRefGoogle ScholarPubMed
80.Morris, JC, Waldmann, TA.Advances in interleukin 2 receptor targeted treatment. Ann Rheum Dis 2000;59(Suppl. 1):i109–i114.CrossRefGoogle ScholarPubMed
81.Yi, H, Zhen, Y, Jiang, L, Zheng, J, Zhao, Y.The phenotypic characterization of naturally occurring regulatory CD4+CD25+ T cells. Cell Mol Immunol 2006;3(3):189–195.Google ScholarPubMed
82.Tchilian, EZ, Beverley, PC.Altered CD45 expression and disease. Trends Immunol 2006;27(3):146–153.CrossRefGoogle ScholarPubMed
83.Svenningsson, A, Andersen, O, Hansson, GK, Stemme, S.Reduced frequency of memory CD8+ T lymphocytes in cerebrospinal fluid and blood of patients with multiple sclerosis. Autoimmunity 1995;21(4):231–239.CrossRefGoogle ScholarPubMed
84.Craddock, RM, Lockstone, HE, Rider, DA, Wayland, MT, Harris, LJ, McKenna, PJ, Bahn, S.Altered T-cell function in schizophrenia: a cellular model to investigate molecular disease mechanisms. PLoS ONE 2007;2:e692.CrossRefGoogle ScholarPubMed
85.Marzio, R, Mauel, J, Betz-Corradin, S. CD69 and regulation of the immune function. Immunopharmacol Immunotoxicol 1999;21(3):565–582.CrossRefGoogle ScholarPubMed
86.Sancho, D, Gomez, M, Sanchez-Madrid, F. CD69 is an immunoregulatory molecule induced following activation. Trends Immunol 2005;26(3):136–140.CrossRefGoogle ScholarPubMed
87.Mihaylova, I, Deruyter, M, Rummens, JL, Bosmans, E, Maes, M.Decreased expression of CD69 in chronic fatigue syndrome in relation to inflammatory markers: evidence for a severe disorder in the early activation of T lymphocytes and natural killer cells. Neuro Endocrinol Lett 2007;28(4).Google ScholarPubMed
88.Bueno, EC, Vaz, AJ, Oliveira, CA, Machado, LR, Livramento, JA, Mielli, SR, Ueda, M.Analysis of cells in cerebrospinal fluid from patients with neurocysticercosis by means of flow cytometry. Cytometry 1999;38(3):106–110.3.0.CO;2-U>CrossRefGoogle ScholarPubMed
89.Kosmaczewska, A, Bilinska, M, Ciszak, L, Noga, L, Pawlak, E, Szteblich, A, Podemski, R, Frydecka, I.Different patterns of activation markers expression and CD4+ T-cell responses to ex vivo stimulation in patients with clinically quiescent multiple sclerosis (MS). J Neuroimmunol 2007.CrossRefGoogle ScholarPubMed
90.Padmos, RC, Bekris, L, Knijff, EM, Tiemeier, H, Kupka, RW, Cohen, Det al.A high prevalence of organ-specific autoimmunity in patients with bipolar disorder. Biol Psychiatry 2004;56:476–482.CrossRefGoogle ScholarPubMed
91.Dantzer, R, Capuron, L, Irwin, MR, Miller, AH, Ollat, H, Perry, VHet al.Identification and treatment of symptoms associated with inflammation in medically ill patients. Psychoneuroendocrinology 2008;33:18–29.CrossRefGoogle ScholarPubMed
92.Potvin, S, Stip, E, Sepehry, AA, Gendron, A, Bah, R, Kouassi, E.Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry 2008;63:801–808.CrossRefGoogle ScholarPubMed
93.Holmes, E, Tsang, TM, Huang, JT, Leweke, FM, Koethe, D, Gerth, CWet al.Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia. PloS Med 2006;3:1420–1427.CrossRefGoogle ScholarPubMed
94.Padmos, RC, Hillegers, MH, Knijff, EM, Vonk, R, Bouvy, A, Staal, FJet al.A discriminating messenger RNA signature for bipolar disorder formed by an aberrant expression of inflammatory genes in monocytes. Arch Gen Psychiatry 2008;65:395–407.CrossRefGoogle ScholarPubMed
95.Mössner, R, Mikova, O, Koutsilieri, E, Saoud, M, Ehlis, AC, Müller, Net al.Consensus paper of the WFSBP task force on biological markers: biological markers in depression. World J Biol Psychiatry 2007;8:141–174.CrossRefGoogle ScholarPubMed
96.Gao, HM, Hong, JS.Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol 2008;29:357–365.CrossRefGoogle ScholarPubMed
97.Medzhitov, R. Origin and physiological roles of inflammation. Nature 2008;454:428–435.CrossRefGoogle ScholarPubMed