Characteristics and critical function of CD8+ T cells in the Toxoplasma-infected brain

Seminars in Immunopathology

Volumn 37, Issue 3, 2015, Pages 261-270

  Landrith, Tyler A ^a   Harris, Tajie H ^b   Wilson, Emma H ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

Author keywords

Blood brain barrier; Brain; Cell behavior; Cell migration; Chemokine; Effector cell; Inflammation; Parasite; Toxoplasma

Indexed keywords

PROGRAMMED DEATH 1 RECEPTOR;

BLOOD BRAIN BARRIER; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; EFFECTOR CELL; ENCEPHALITIS; HOST PARASITE INTERACTION; HUMAN; IMMUNOCOMPROMISED PATIENT; IMMUNOREGULATION; INFECTION CONTROL; LYMPHOCYTE FUNCTION; LYMPHOCYTIC INFILTRATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PARASITE CLEARANCE; PHENOTYPIC VARIATION; PRIORITY JOURNAL; PROTOZOAL ENTRY; REVIEW; T CELL DEPLETION; TOXOPLASMA GONDII; TOXOPLASMIC ENCEPHALITIS; TOXOPLASMOSIS; ANIMAL; ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; CEREBRAL TOXOPLASMOSIS; IMMUNE EVASION; IMMUNOLOGY; METABOLISM; PARASITOLOGY; PHENOTYPE; T LYMPHOCYTE SUBPOPULATION; TOXOPLASMA;

ANIMALS; ANTIGEN PRESENTATION; ANTIGEN-PRESENTING CELLS; CD8-POSITIVE T-LYMPHOCYTES; HOST-PARASITE INTERACTIONS; HUMANS; IMMUNE EVASION; PHENOTYPE; T-LYMPHOCYTE SUBSETS; TOXOPLASMA; TOXOPLASMOSIS, CEREBRAL;

EID: 84929842056     PISSN: 18632297     EISSN: 18632300     Source Type: Journal    
DOI: 10.1007/s00281-015-0487-3     Document Type: Review

References (77)

1. Carruthers V, Boothroyd JC (2007) Pulling together: an integrated model of Toxoplasma cell invasion. Curr Opin Microbiol 10(1):83–89. doi:10.1016/j.mib.2006.06.017
2. Pappas G, Roussos N, Falagas ME (2009) Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. Int J Parasitol 39(12):1385–1394. doi:10.1016/j.ijpara.2009.04.003
3. Luft BJ, Brooks RG, Conley FK, McCabe RE, Remington JS (1984) Toxoplasmic encephalitis in patients with acquired immune deficiency syndrome. JAMA 252(7):913–917
4. Luft BJ, Remington JS (1988) AIDS commentary. Toxoplasmic encephalitis. J Infect Dis 157(1):1–6
5. Suzuki Y, Conley FK, Remington JS (1989) Importance of endogenous IFN-gamma for prevention of toxoplasmic encephalitis in mice. J Immunol 143(6):2045–2050
6. Gazzinelli R, Xu Y, Hieny S, Cheever A, Sher A (1992) Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii. J Immunol 149(1):175–180
7. Dellacasa-Lindberg I, Hitziger N, Barragan A (2007) Localized recrudescence of Toxoplasma infections in the central nervous system of immunocompromised mice assessed by in vivo bioluminescence imaging. Microbes Infect 9(11):1291–1298. doi:10.1016/j.micinf.2007.06.003
8. Saeij JP, Boyle JP, Grigg ME, Arrizabalaga G, Boothroyd JC (2005) Bioluminescence imaging of Toxoplasma gondii infection in living mice reveals dramatic differences between strains. Infect Immun 73(2):695–702. doi:10.1128/IAI. 73.2.695-702.2005
9. Barcan LA, Dallurzo ML, Clara LO, Valledor A, Macias S, Zorkin E, Gerona S, Livellara B (2002) Toxoplasma gondii pneumonia in liver transplantation: survival after a severe case of reactivation. Transpl Infect Dis 4(2):93–96
10. Hermes G, Ajioka JW, Kelly KA, Mui E, Roberts F, Kasza K, Mayr T, Kirisits MJ, Wollmann R, Ferguson DJ, Roberts CW, Hwang JH, Trendler T, Kennan RP, Suzuki Y, Reardon C, Hickey WF, Chen L, McLeod R (2008) Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection. J Neuroinflammation 5:48. doi:10.1186/1742-2094-5-48
11. Koshy AA, Fouts AE, Lodoen MB, Alkan O, Blau HM, Boothroyd JC (2010) Toxoplasma secreting Cre recombinase for analysis of host-parasite interactions. Nat Methods 7 (4):307–309. doi: 10.1038/nmeth.1438
12. Melzer TC, Cranston HJ, Weiss LM, Halonen SK (2010) Host cell preference of Toxoplasma gondii cysts in murine brain: a confocal study. J Neuroparasitology 1. doi:10.4303/jnp/N100505
13. Wilson EH, Weninger W, Hunter CA (2010) Trafficking of immune cells in the central nervous system. J Clin Invest 120(5):1368–1379. doi:10.1172/JCI41911
14. Schluter D, Hein A, Dorries R, Deckert-Schluter M (1995) Different subsets of T cells in conjunction with natural killer cells, macrophages, and activated microglia participate in the intracerebral immune response to Toxoplasma gondii in athymic nude and immunocompetent rats. Am J Pathol 146(4):999–1007
15. John B, Ricart B, Tait Wojno ED, Harris TH, Randall LM, Christian DA, Gregg B, De Almeida DM, Weninger W, Hammer DA, Hunter CA (2011) Analysis of behavior and trafficking of dendritic cells within the brain during toxoplasmic encephalitis. PLoS Pathog 7(9):e1002246. doi:10.1371/journal.ppat.1002246
16. Suzuki Y, Sa Q, Gehman M, Ochiai E (2011) Interferon-gamma- and perforin-mediated immune responses for resistance against Toxoplasma gondii in the brain. Expert Rev Mol Med 13:e31. doi:10.1017/S1462399411002018
17. Brown CR, Hunter CA, Estes RG, Beckmann E, Forman J, David C, Remington JS, McLeod R (1995) Definitive identification of a gene that confers resistance against Toxoplasma cyst burden and encephalitis. Immunology 85(3):419–428
18. Kim JV, Kang SS, Dustin ML, McGavern DB (2009) Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature 457(7226):191–195. doi:10.1038/nature07591
19. Frevert U, Nacer A (2014) Fatal cerebral malaria: a venous efflux problem. Front Cell Infect Microbiol 4:155. doi:10.3389/fcimb.2014.00155
20. Silva NM, Manzan RM, Carneiro WP, Milanezi CM, Silva JS, Ferro EA, Mineo JR (2010) Toxoplasma gondii: the severity of toxoplasmic encephalitis in C57BL/6 mice is associated with increased ALCAM and VCAM-1 expression in the central nervous system and higher blood–brain barrier permeability. Exp Parasitol 126 (2):167–177. doi:10.1016/j.exppara.2010.04.019
21. Deckert-Schluter M, Schluter D, Hof H, Wiestler OD, Lassmann H (1994) Differential expression of ICAM-1, VCAM-1 and their ligands LFA-1, Mac-1, CD43, VLA-4, and MHC class II antigens in murine Toxoplasma encephalitis: a light microscopic and ultrastructural immunohistochemical study. J Neuropathol Exp Neurol 53(5):457–468
22. Wang X, Michie SA, Xu B, Suzuki Y (2007) Importance of IFN-gamma-mediated expression of endothelial VCAM-1 on recruitment of CD8+ T cells into the brain during chronic infection with Toxoplasma gondii. J Interferon Cytokine Res 27(4):329–338. doi:10.1089/jir.2006.0154
23. Carrithers MD, Visintin I, Kang SJ, Janeway CA Jr (2000) Differential adhesion molecule requirements for immune surveillance and inflammatory recruitment. Brain 123(Pt 6):1092–1101
24. Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N (1992) Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356(6364):63–66. doi:10.1038/356063a0
25. Engelhardt B, Kappos L (2008) Natalizumab: targeting alpha4-integrins in multiple sclerosis. Neurodegener Dis 5(1):16–22. doi:10.1159/000109933
26. Wilson EH, Harris TH, Mrass P, John B, Tait ED, Wu GF, Pepper M, Wherry EJ, Dzierzinski F, Roos D, Haydon PG, Laufer TM, Weninger W, Hunter CA (2009) Behavior of parasite-specific effector CD8+ T cells in the brain and visualization of a kinesis-associated system of reticular fibers. Immunity 30(2):300–311. doi:10.1016/j.immuni.2008.12.013
27. Sa Q, Ochiai E, Sengoku T, Wilson ME, Brogli M, Crutcher S, Michie SA, Xu B, Payne L, Wang X, Suzuki Y (2014) VCAM-1/alpha4beta1 integrin interaction is crucial for prompt recruitment of immune T cells into the brain during the early stage of reactivation of chronic infection with Toxoplasma gondii to prevent toxoplasmic encephalitis. Infect Immun 82(7):2826–2839. doi:10.1128/IAI. 01494-13
28. Williams DW, Calderon TM, Lopez L, Carvallo-Torres L, Gaskill PJ, Eugenin EA, Morgello S, Berman JW (2013) Mechanisms of HIV entry into the CNS: increased sensitivity of HIV infected CD14+CD16+ monocytes to CCL2 and key roles of CCR2, JAM-A, and ALCAM in diapedesis. PLoS One 8 (7):e69270. doi:10.1371/journal.pone.0069270
29. Sathiyanadan K, Coisne C, Enzmann G, Deutsch U, Engelhardt B (2014) PSGL-1 and E/P-selectins are essential for T-cell rolling in inflamed CNS microvessels but dispensable for initiation of EAE. Eur J Immunol 44 (8):2287–2294. doi:10.1002/eji.201344214
30. Schneider-Hohendorf T, Rossaint J, Mohan H, Boning D, Breuer J, Kuhlmann T, Gross CC, Flanagan K, Sorokin L, Vestweber D, Zarbock A, Schwab N, Wiendl H (2014) VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells. J Exp Med 211 (9):1833–1846. doi:10.1084/jem.20140540
31. Forster R, Davalos-Misslitz AC, Rot A (2008) CCR7 and its ligands: balancing immunity and tolerance. Nat Rev Immunol 8(5):362–371. doi:10.1038/nri2297
32. Noor S, Habashy AS, Nance JP, Clark RT, Nemati K, Carson MJ, Wilson EH (2010) CCR7-dependent immunity during acute Toxoplasma gondii infection. Infect Immun 78(5):2257–2263. doi:10.1128/IAI. 01314-09
33. Ploix CC, Noor S, Crane J, Masek K, Carter W, Lo DD, Wilson EH, Carson MJ (2011) CNS-derived CCL21 is both sufficient to drive homeostatic CD4+ T cell proliferation and necessary for efficient CD4+ T cell migration into the CNS parenchyma following Toxoplasma gondii infection. Brain Behav Immun 25(5):883–896. doi:10.1016/j.bbi.2010.09.014
34. Christensen JE, Nansen A, Moos T, Lu B, Gerard C, Christensen JP, Thomsen AR (2004) Efficient T-cell surveillance of the CNS requires expression of the CXC chemokine receptor 3. J Neurosci 24(20):4849–4858. doi:10.1523/JNEUROSCI. 0123-04.2004
35. Muller M, Carter SL, Hofer MJ, Manders P, Getts DR, Getts MT, Dreykluft A, Lu B, Gerard C, King NJ, Campbell IL (2007) CXCR3 signaling reduces the severity of experimental autoimmune encephalomyelitis by controlling the parenchymal distribution of effector and regulatory T cells in the central nervous system. J Immunol 179(5):2774–2786
36. Kivisakk P, Trebst C, Liu Z, Tucky BH, Sorensen TL, Rudick RA, Mack M, Ransohoff RM (2002) T-cells in the cerebrospinal fluid express a similar repertoire of inflammatory chemokine receptors in the absence or presence of CNS inflammation: implications for CNS trafficking. Clin Exp Immunol 129(3):510–518
37. Zhang B, Chan YK, Lu B, Diamond MS, Klein RS (2008) CXCR3 mediates region-specific antiviral T cell trafficking within the central nervous system during West Nile virus encephalitis. J Immunol 180(4):2641–2649
38. Klein RS, Lin E, Zhang B, Luster AD, Tollett J, Samuel MA, Engle M, Diamond MS (2005) Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis. J Virol 79(17):11457–11466. doi:10.1128/JVI. 79.17.11457-11466.2005
39. Brunn A, Montesinos-Rongen M, Strack A, Reifenberger G, Mawrin C, Schaller C, Deckert M (2007) Expression pattern and cellular sources of chemokines in primary central nervous system lymphoma. Acta Neuropathol 114(3):271–276. doi:10.1007/s00401-007-0258-x
40. Strack A, Schluter D, Asensio VC, Campbell IL, Deckert M (2002) Regulation of the kinetics of intracerebral chemokine gene expression in murine Toxoplasma encephalitis: impact of host genetic factors. Glia 40(3):372–377. doi:10.1002/glia.10104
41. Harris TH, Banigan EJ, Christian DA, Konradt C, Tait Wojno ED, Norose K, Wilson EH, John B, Weninger W, Luster AD, Liu AJ, Hunter CA (2012) Generalized Levy walks and the role of chemokines in migration of effector CD8+ T cells. Nature 486(7404):545–548. doi:10.1038/nature11098
42. Galea I, Bernardes-Silva M, Forse PA, van Rooijen N, Liblau RS, Perry VH (2007) An antigen-specific pathway for CD8 T cells across the blood–brain barrier. J Exp Med 204(9):2023–2030. doi:10.1084/jem.20070064
43. Kang SS, Herz J, Kim JV, Nayak D, Stewart-Hutchinson P, Dustin ML, McGavern DB (2011) Migration of cytotoxic lymphocytes in cell cycle permits local MHC I-dependent control of division at sites of viral infection. J Exp Med 208(4):747–759. doi:10.1084/jem.20101295
44. Lodygin D, Odoardi F, Schlager C, Korner H, Kitz A, Nosov M, van den Brandt J, Reichardt HM, Haberl M, Flugel A (2013) A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T cell activation in real time during CNS autoimmunity. Nat Med 19(6):784–790. doi:10.1038/nm.3182
45. Bartholomaus I, Kawakami N, Odoardi F, Schlager C, Miljkovic D, Ellwart JW, Klinkert WE, Flugel-Koch C, Issekutz TB, Wekerle H, Flugel A (2009) Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 462(7269):94–98. doi:10.1038/nature08478
46. Truong P, Heydari S, Garidou L, McGavern DB (2009) Persistent viral infection elevates central nervous system MHC class I through chronic production of interferons. J Immunol 183(6):3895–3905. doi:10.4049/jimmunol.0803085
47. Barcia C, Sanderson NS, Barrett RJ, Wawrowsky K, Kroeger KM, Puntel M, Liu C, Castro MG, Lowenstein PR (2008) T cells’ immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury. PLoS One 3(8):e2977. doi:10.1371/journal.pone.0002977
48. Barcia C, Wawrowsky K, Barrett RJ, Liu C, Castro MG, Lowenstein PR (2008) In vivo polarization of IFN-gamma at Kupfer and non-Kupfer immunological synapses during the clearance of virally infected brain cells. J Immunol 180(3):1344–1352
49. Chtanova T, Schaeffer M, Han SJ, van Dooren GG, Nollmann M, Herzmark P, Chan SW, Satija H, Camfield K, Aaron H, Striepen B, Robey EA (2008) Dynamics of neutrophil migration in lymph nodes during infection. Immunity 29(3):487–496. doi:10.1016/j.immuni.2008.07.012
50. Schaeffer M, Han SJ, Chtanova T, van Dooren GG, Herzmark P, Chen Y, Roysam B, Striepen B, Robey EA (2009) Dynamic imaging of T cell-parasite interactions in the brains of mice chronically infected with Toxoplasma gondii. J Immunol 182(10):6379–6393. doi:10.4049/jimmunol.0804307
51. Nair A, Frederick TJ, Miller SD (2008) Astrocytes in multiple sclerosis: a product of their environment. Cell Mol Life Sci 65(17):2702–2720. doi:10.1007/s00018-008-8059-5
52. Lalor SJ, Segal BM (2010) Lymphoid chemokines in the CNS. J Neuroimmunol 224(1–2):56–61. doi:10.1016/j.jneuroim.2010.05.017
53. Banigan EJ, Harris TH, Christian DA, Hunter CA, Liu AJ (2015) Heterogeneous CD8+ T cell migration in the lymph node in the absence of inflammation revealed by quantitative migration analysis. PLoS Comput Biol 11 (2):e1004058. doi:10.1371/journal.pcbi.1004058
54. Kang H, Liesenfeld O, Remington JS, Claflin J, Wang X, Suzuki Y (2003) TCR V beta 8+ T cells prevent development of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease. J Immunol 170(8):4254–4259
55. Suzuki Y, Wang X, Jortner BS, Payne L, Ni Y, Michie SA, Xu B, Kudo T, Perkins S (2010) Removal of Toxoplasma gondii cysts from the brain by perforin-mediated activity of CD8+ T cells. Am J Pathol 176(4):1607–1613. doi:10.2353/ajpath.2010.090825
56. Wang X, Claflin J, Kang H, Suzuki Y (2005) Importance of CD8(+)Vbeta8(+) T cells in IFN-gamma-mediated prevention of toxoplasmic encephalitis in genetically resistant BALB/c mice. J Interferon Cytokine Res 25(6):338–344. doi:10.1089/jir.2005.25.338
57. Denkers EY, Yap G, Scharton-Kersten T, Charest H, Butcher BA, Caspar P, Heiny S, Sher A (1997) Perforin-mediated cytolysis plays a limited role in host resistance to Toxoplasma gondii. J Immunol 159(4):1903–1908
58. Coombes JL, Robey EA (2010) Dynamic imaging of host-pathogen interactions in vivo. Nat Rev Immunol 10 (5):353–364. doi:10.1038/nri2746
59. Nance JP, Vannella KM, Worth D, David C, Carter D, Noor S, Hubeau C, Fitz L, Lane TE, Wynn TA, Wilson EH (2012) Chitinase dependent control of protozoan cyst burden in the brain. PLoS Pathog 8 (11):e1002990. doi:10.1371/journal.ppat.1002990
60. Frickel EM, Sahoo N, Hopp J, Gubbels MJ, Craver MP, Knoll LJ, Ploegh HL, Grotenbreg GM (2008) Parasite stage-specific recognition of endogenous Toxoplasma gondii-derived CD8+ T cell epitopes. J Infect Dis 198(11):1625–1633. doi:10.1086/593019
61. Dupont CD, Christian DA, Selleck EM, Pepper M, Leney-Greene M, Harms Pritchard G, Koshy AA, Wagage S, Reuter MA, Sibley LD, Betts MR, Hunter CA (2014) Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii. PLoS Pathog 10(4):e1004047. doi:10.1371/journal.ppat.1004047
62. Schluter D, Meyer T, Kwok LY, Montesinos-Rongen M, Lutjen S, Strack A, Schmitz ML, Deckert M (2002) Phenotype and regulation of persistent intracerebral T cells in murine Toxoplasma encephalitis. J Immunol 169(1):315–322
63. Zinselmeyer BH, Heydari S, Sacristan C, Nayak D, Cammer M, Herz J, Cheng X, Davis SJ, Dustin ML, McGavern DB (2013) PD-1 promotes immune exhaustion by inducing antiviral T cell motility paralysis. J Exp Med 210(4):757–774. doi:10.1084/jem.20121416
64. Bhadra R, Khan IA (2012) Redefining chronic toxoplasmosis—a T cell exhaustion perspective. PLoS Pathog 8(10):e1002903. doi:10.1371/journal.ppat.1002903
65. Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, Kalia V, Subramaniam S, Blattman JN, Barber DL, Ahmed R (2007) Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 27(4):670–684. doi:10.1016/j.immuni.2007.09.006
66. Bhadra R, Gigley JP, Weiss LM, Khan IA (2011) Control of Toxoplasma reactivation by rescue of dysfunctional CD8+ T-cell response via PD-1-PDL-1 blockade. Proc Natl Acad Sci U S A 108(22):9196–9201. doi:10.1073/pnas.1015298108
67. Bhadra R, Cobb DA, Khan IA (2013) Donor CD8+ T cells prevent Toxoplasma gondii de-encystation but fail to rescue the exhausted endogenous CD8+ T cell population. Infect Immun 81(9):3414–3425. doi:10.1128/IAI. 00784-12
68. Shin H, Blackburn SD, Blattman JN, Wherry EJ (2007) Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection. J Exp Med 204(4):941–949. doi:10.1084/jem.20061937
69. Wakim LM, Woodward-Davis A, Bevan MJ Memory T (2010) cells persisting within the brain after local infection show functional adaptations to their tissue of residence. Proc Natl Acad Sci U S A 107 (42):17872–17879. doi: 10.1073/pnas.1010201107
70. Becker TC, Wherry EJ, Boone D, Murali-Krishna K, Antia R, Ma A, Ahmed R (2002) Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J Exp Med 195(12):1541–1548
71. Schluns KS, Kieper WC, Jameson SC, Lefrancois L (2000) Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat Immunol 1(5):426–432. doi:10.1038/80868
72. Khan IA, Casciotti L (1999) IL-15 prolongs the duration of CD8+ T cell-mediated immunity in mice infected with a vaccine strain of Toxoplasma gondii. J Immunol 163(8):4503–4509
73. Lieberman LA, Villegas EN, Hunter CA (2004) Interleukin-15-deficient mice develop protective immunity to Toxoplasma gondii. Infect Immun 72(11):6729–6732. doi:10.1128/IAI. 72.11.6729-6732.2004
74. Bhadra R, Guan H, Khan IA (2010) Absence of both IL-7 and IL-15 severely impairs the development of CD8 T cell response against Toxoplasma gondii. PLoS One 5(5):e10842. doi:10.1371/journal.pone.0010842
75. Sauer BM, Schmalstieg WF, Howe CL (2013) Axons are injured by antigen-specific CD8(+) T cells through a MHC class I- and granzyme B-dependent mechanism. Neurobiol Dis 59:194–205. doi:10.1016/j.nbd.2013.07.010
76. Drogemuller K, Helmuth U, Brunn A, Sakowicz-Burkiewicz M, Gutmann DH, Mueller W, Deckert M, Schluter D (2008) Astrocyte gp130 expression is critical for the control of Toxoplasma encephalitis. J Immunol 181(4):2683–2693
77. Sosa RA, Murphey C, Ji N, Cardona AE, Forsthuber TG (2013) The kinetics of myelin antigen uptake by myeloid cells in the central nervous system during experimental autoimmune encephalomyelitis. J Immunol 191 (12):5848–5857. doi: 10.4049/jimmunol.1300771