Challenging the role of adaptive immunity in neurotrauma: Rag1 -/- mice lacking mature B and T cells do not show neuroprotection after closed head injury

Journal of Neurotrauma

Volumn 29, Issue 6, 2012, Pages 1233-1242

  Weckbach, Sebastian ^a   Neher, Miriam ^a   Losacco, Justin T ^a   Bolden, Ashley L ^a   Kulik, Liudmila ^a   Flierl, Michael A ^a   Bell, Scott E ^a   Holers, V Michael ^a   Stahel, Philip F ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

adaptive immunity; closed head injury; complement system; natural antibodies; Rag1

Indexed keywords

COMPLEMENT COMPONENT C3A; FAS ANTIGEN; FAS LIGAND; INTERLEUKIN 10; INTERLEUKIN 6; PROTEIN BAX; PROTEIN BCL 2; RAG1 PROTEIN; TUMOR NECROSIS FACTOR ALPHA;

ADAPTIVE IMMUNITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; ASTROCYTOSIS; B LYMPHOCYTE; BLOOD BRAIN BARRIER; BRAIN TISSUE; CONTROLLED STUDY; HEAD INJURY; HISTOPATHOLOGY; INFLAMMATION; INJURY SEVERITY; INNATE IMMUNITY; MOUSE; NERVE CELL NECROSIS; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PATHOPHYSIOLOGY; T LYMPHOCYTE; TISSUE INJURY;

ADAPTIVE IMMUNITY; ANIMALS; B-LYMPHOCYTES; BLOOD-BRAIN BARRIER; BLOTTING, WESTERN; COMPLEMENT ACTIVATION; GENES, RAG-1; HEAD INJURIES, CLOSED; IMMUNOHISTOCHEMISTRY; IN SITU NICK-END LABELING; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; T-LYMPHOCYTES;

EID: 84859912177     PISSN: 08977151     EISSN: 15579042     Source Type: Journal    
DOI: 10.1089/neu.2011.2169     Document Type: Article

References (72)

1. Alexander, J.J., Anderson, A.J., Barnum, S.R., Stevens, B., and Tenner, A.J. (2008). The complement cascade: Yin-Yang in neuroinflammation, neuroprotection, and degeneration. J. Neurochem. 107, 1169-1187.
2. Ankeny, D.P., Guan, Z., and Popovich, P.G. (2009). B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice. J. Clin. Invest. 119, 2990-2999.
3. Austen, W.G., Jr., Zhang, M., Chan, R., Friend, D., Hechtman, H.B., Carroll, M.C., and Moore, F.D., Jr. (2004). Murine hindlimb reperfusion injury can be initiated by a self-reactive monoclonal IgM. Surgery 136, 401-406. (Pubitemid 39037680)
4. Beauchamp, K., Mutlak, H., Smith, W.R., Shohami, E., and Stahel, P.F. (2008). Pharmacology of traumatic brain injury: where is the ''golden bullet''? Mol. Med. 14, 731-740.
5. Bechmann, I., Galea, I., and Perry, V.H. (2007). What is the blood-brain barrier (not)? Trends Immunol. 28, 5-11. (Pubitemid 46001619)
6. Bellander, B.M., Lidman, O., Ohlsson, M., Meijer, B., Piehl, F., and Svensson, M. (2010). Genetic regulation of microglia activation, complement expression, and neurodegeneration in a rat model of traumatic brain injury. Exp. Brain Res. 205, 103-114.
7. Bellander, B.M., Olafsson, I.H., Ghatan, P.H., Bro Skejo, H.P., Hansson, L.O., Wanecek, M., and Svensson, M.A. (2011). Secondary insults following traumatic brain injury enhance complement activation in the human brain and release of the tissue damage marker S100B. Acta Neurochir. (Wien.) 153, 90-100.
8. Beni-Adani, L., Gozes, I., Cohen, Y., Assaf, Y., Steingart, R.A., Brenneman, D.E., Eizenberg, O., Trembolver, V., and Shohami, E. (2001). A peptide derived from activity-dependent neuroprotective protein (ADNP) ameliorates injury response in closed head injury in mice. J. Pharmacol. Exp. Ther. 296, 57-63. (Pubitemid 32015060)
9. Biagas, K.V., Uhl, M.W., Schiding, J.K., Nemoto, E.M., and Kochanek, P.M. (1992). Assessment of posttraumatic polymorphonuclear leukocyte accumulation in rat brain using tissue myeloperoxidase assay and vinblastine treatment. J. Neurotrauma 9, 363-371. (Pubitemid 23031061)
10. Carroll, M.C. (2004). The complement system in regulation of adaptive immunity. Nat. Immunol. 5, 981-986. (Pubitemid 41057714)
11. Cederberg, D., and Siesjo, P. (2010). What has inflammation to do with traumatic brain injury? Childs Nerv. Syst. 26, 221-226.
12. Chen, Y., Constantini, S., Trembovler, V., Weinstock, M., and Shohami, E. (1996). An experimental model of closed head injury in mice: pathophysiology, histopathology, and cognitive deficits. J. Neurotrauma 13, 557-568. (Pubitemid 26377854)
13. Clausen, F., Lorant, T., Lewen, A., and Hillered, L. (2007). T lymphocyte trafficking: a novel target for neuroprotection in traumatic brain injury. J. Neurotrauma 24, 1295-1307. (Pubitemid 47340090)
14. Czigner, A., Mihaly, A., Farkas, O., Buki, A., Krisztin-Peva, B., Dobo, E., and Barzo, P. (2007). Kinetics of the cellular immune response following closed head injury. Acta Neurochir. (Wien.) 149, 281-289. (Pubitemid 46365419)
15. Dimayuga, P.C., Cesena, F.H., Chyu, K.Y., Yano, J., Amorn, A., Fishbein, M.C., Shah, P.K., and Cercek, B. (2009). Natural antibodies and complement modulate intimal thickening after arterial injury. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R1593-R1600.
16. Elward, K., and Gasque, P. (2003). ''Eat me'' and ''don't eat me'' signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system. Mol. Immunol. 40, 85-94. (Pubitemid 36959819)
17. Engelhardt, B., and Coisne, C. (2011). Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle. Fluids Barriers CNS 8, 4.
18. Farkas, I.G., Czigner, A., Farkas, E., Dobo, E., Soos, K., Penke, B., Endresz, V., and Mihaly, A. (2003). Beta-amyloid peptideinduced blood-brain barrier disruption facilitates T-cell entry into the rat brain. Acta Histochem. 105, 115-125. (Pubitemid 36734149)
19. Fee, D., Crumbaugh, A., Jacques, T., Herdrich, B., Sewell, D., Auerbach, D., Piaskowski, S., Hart, M.N., Sandor, M., and Fabry, Z. (2003). Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury. J. Neuroimmunol. 136, 54-66. (Pubitemid 36298844)
20. Finsen, B., and Owens, T. (2011). Innate immune responses in central nervous system inflammation. FEBS Lett. [May 27; Epub ahead of print]).
21. Fleming, S.D., Egan, R.P., Chai, C., Girardi, G., Holers, V.M., Salmon, J., Monestier, M., and Tsokos, G.C. (2004). Antiphospholipid antibodies restore mesenteric ischemia/reperfusion-induced injury in complement receptor 2/complement receptor 1-deficient mice. J. Immunol. 173, 7055-7061. (Pubitemid 39541095)
22. Fleming, S.D. (2006). Natural antibodies, autoantibodies and complement activation in tissue injury. Autoimmunity 39, 379-386. (Pubitemid 44269615)
23. Fleming, S.D., Shea-Donohue, T., Guthridge, J.M., Kulik, L., Waldschmidt, T.J., Gipson, M.G., Tsokos, G.C., and Holers, V.M. (2002). Mice deficient in complement receptors 1 and 2 lack a tissue injury-inducing subset of the natural antibody repertoire. J. Immunol. 169, 2126-2133. (Pubitemid 34857679)
24. Flierl, M.A., Stahel, P.F., Beauchamp, K.M., Morgan, S.J., Smith, W.R., and Shohami, E. (2009). Mouse closed head injury model induced by a weight-drop device. Nat. Protoc. 4, 1328-1337.
25. Francis, K., van Beek, J., Canova, C., Neal, J.W., and Gasque, P. (2003). Innate immunity and brain inflammation: the key role of complement. Expert Rev. Mol. Med. 5, 1-19.
26. Galea, I., Bechmann, I., and Perry, V.H. (2007a). What is immune privilege (not)? Trends Immunol. 28, 12-18. (Pubitemid 44960159)
27. Galea, I., Bernardes-Silva, M., Forse, P.A., van Rooijen, N., Liblau, R.S., and Perry, V.H. (2007b). An antigen-specific pathway for CD8 T cells across the blood-brain barrier. J. Exp. Med. 204, 2023-2030. (Pubitemid 47360864)
28. Gasque, P. (2004). Complement: a unique innate immune sensor for danger signals. Mol. Immunol. 41, 1089-1098. (Pubitemid 39345390)
29. Gong, N., Liu, J., Reynolds, A.D., Gorantla, S., Mosley, R.L., and Gendelman, H.E. (2011). Brain ingress of regulatory T cells in a murine model of HIV-1 encephalitis. J. Neuroimmunol. 230, 33-41.
30. Griffiths, M.R., Gasque, P., and Neal, J.W. (2010). The regulation of the CNS innate immune response is vital for the restoration of tissue homeostasis (repair) after acute brain injury: a brief review. Int. J. Inflam. 2010, 151097.
31. Ha, G.K., Hunag, Z., Streit, W.J., and Petitto, J.M. (2006). Endogenous T lymphocytes and microglial reactivity in the axotomized facial motor nucleus of mice: Effect of genetic background and the RAG2 gene. J. Neuroimmunol. 172, 1-8. (Pubitemid 43277486)
32. Harhausen, D., Khojasteh, U., Stahel, P.F., Morgan, B.P., Nietfeld, W., Dirnagl, U., and Trendelenburg, G. (2010). Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice. J. Neuroinflammation 7, 15.
33. Hazlett, L.D., and Hendricks, R.L. (2010). Reviews for immune privilege in the year 2010: immune privilege and infection. Ocul. Immunol. Inflamm. 18, 237-243.
34. Hendrix, S., and Nitsch, R. (2007). The role of T helper cells in neuroprotection and regeneration. J. Neuroimmunol. 184, 100-112. (Pubitemid 46365994)
35. Hickey, W.F. (1999). Leukocyte traffic in the central nervous system: the participants and their roles. Semin. Immunol. 11, 125-137. (Pubitemid 29201818)
36. Hickey, W.F. (1991). Migration of hematogenous cells through the blood-brain barrier and the initiation of CNS inflammation. Brain Pathol. 1, 97-105.
37. Holers, V.M., and Kulik, L. (2007). Complement receptor 2, natural antibodies and innate immunity: Inter-relationships in B cell selection and activation. Mol. Immunol. 44, 64-72. (Pubitemid 44647113)
38. Holers, V.M. (2005). Complement receptors and the shaping of the natural antibody repertoire. Springer Semin. Immunopathol. 26, 405-423. (Pubitemid 40468893)
39. Hu, Z., Li, Y., Fang, M., Wai, M.S., and Yew, D.T. (2009). Exogenous progesterone: a potential therapeutic candidate in CNS injury and neurodegeneration. Curr. Med. Chem. 16, 1418-1425.
40. Kipnis, J., Nevo, U., Panikashvili, D., Alexandrovich, A., Yoles, E., Akselrod, S., Shohami, E., and Schwartz, M. (2003). Therapeutic vaccination for closed head injury. J. Neurotrauma 20, 559-569. (Pubitemid 36807900)
41. Kulik, L., Fleming, S.D., Moratz, C., Reuter, J.W., Novikov, A., Chen, K., Andrews, K.A., Markaryan, A., Quigg, R.J., Silverman, G.J., Tsokos, G.C., and Holers, V.M. (2009). Pathogenic natural antibodies recognizing annexin IV are required to develop intestinal ischemia-reperfusion injury. J. Immunol. 182, 5363-5373.
42. Leinhase, I., Holers, V.M., Thurman, J.M., Harhausen, D., Schmidt, O.I., Pietzcker, M., Taha, M.E., Rittirsch, D., Huber- Lang, M., Smith, W.R., Ward, P.A., and Stahel, P.F. (2006a). Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation. BMC Neurosci. 7, 55.
43. Leinhase, I, Schmidt, O.I., Thurman, J.M., Hossini, A.M., Rozanski, M., Taha, M.E., Scheffler, A., John, T., Smith, W.R., Holers, V.M., and Stahel, P.F. (2006b). Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury. Exp. Neurol. 199, 454-464. (Pubitemid 44202458)
44. Liesz, A., Suri-Payer, E., Veltkamp, C., Doerr, H., Sommer, C., Rivest, S., Giese, T., and Veltkamp, R. (2009). Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat. Med. 15, 192-199.
45. Lindner, V., and Heinle, H. (1982). Binding properties of circulating Evans blue in rabbits as determined by disc electrohporesis. Atherosclerosis 43, 417-422. (Pubitemid 12073506)
46. Loane, D.J., and Faden, A.I. (2010). Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends Pharmacol. Sci. 31, 596-604.
47. Mombaerts, P., Iacomini, J., Johnson, R.S., Herrup, K., Tonegawa, S., and Papaioannou, V.E. (1992). RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68, 869-877.
48. Mombaerts, P. (1995). Lymphocyte development and function in T-cell receptor and RAG-1 mutant mice. Int. Rev. Immunol. 13, 43-63.
49. Morgan, B.P., Marchbank, K.J., Longhi, M.P., Harris, C.L., and Gallimore, A.M. (2005). Complement: central to innate immunity and bridging to adaptive responses. Immunol. Lett. 97, 171-179. (Pubitemid 40326948)
50. Morganti-Kossmann, M.C., Rancan, M., Stahel, P.F., and Kossmann, T. (2002). Inflammatory response in acute traumatic brain injury: a double-edged sword. Curr. Opin. Crit. Care 8, 101-105. (Pubitemid 36132681)
51. Morganti-Kossmann, M.C., Yan, E., and Bye, N. (2010). Animal models of traumatic brain injury: Is there an optimal model to reproduce human brain injury in the laboratory? Injury 41 (Suppl.), S10-S13.
52. Otto, V.I., Stahel, P.F., Rancan, M., Kariya, K., Shohami, E., Yatsiv, I., Eugster, H.P., Kossmann, T., Trentz, O., and Morganti-Kossmann, M.C. (2001). Regulation of chemokines and chemokine receptors after experimental closed head injury. Neuroreport 12, 2059-2064. (Pubitemid 32553731)
53. Pachter, J.S., de Vries, H.E., and Fabry, Z. (2003). The bloodbrain barrier and its role in immune privilege in the central nervous system. J. Neuropathol. Exp. Neurol. 62, 593-604. (Pubitemid 36682632)
54. Perry, V.H. (1998). A revised view of the central nervous system microenvironment and major histocompatibility complex class II antigen presentation. J. Neuroimmunol. 90, 113-121.
55. Qiao, F., Atkinson, C., Song, H., Pannu, R., Singh, I., and Tomlinson, S. (2006). Complement plays an important role in spinal cord injury and represents a therapeutic target for improving recovery following trauma. Am. J. Pathol. 169, 1039-1047. (Pubitemid 44411965)
56. Ramlackhansingh, A.F., Brooks, D.J., Greenwood, R.J., Bose, S.K., Turkheimer, F.E., Kinnunen, K.M., Gentleman, S., Heckemann, R.A., Gunanayagam, K., Gelosa, G., and Sharp, D.J. (2011). Inflammation after trauma: Microglial activation and traumatic brain injury. Ann. Neurol. [April 18; Epub ahead of print].
57. Rancan, M., Morganti-Kossmann, M.C., Barnum, S.R., Saft, S., Schmidt, O.I., Ertel, W., and Stahel, P.F. (2003). Central nervous system-targeted complement inhibition mediates neuroprotection after closed head injury in transgenic mice. J. Cereb. Blood Flow Metab. 23, 1070-1074. (Pubitemid 37082432)
58. Reid, R.R., Woodcock, S., Shimabukuro-Vornhagen, A., Austen, W.G., Jr., Kobzik, L., Zhang, M., Hechtman, H.B., Moore, F.D., Jr., and Carroll, M.C. (2002). Functional activity of natural antibody is altered in Cr2-deficient mice. J. Immunol. 169, 5433-5440. (Pubitemid 35291640)
59. Rhodes, J. (2011). Peripheral immune cells in the pathology of traumatic brain injury? Curr. Opin. Crit. Care 17, 122-130.
60. Sayed, B.A., Christy, A.L., Walker, M.E., and Brown, M.A. (2011). Meningeal mast cells affect early T cell central nervous system infiltration and blood-brain barrier integrity through TNF: a role for neutrophil recruitment? J. Immunol. 184, 6891-6900.
61. Schwartz, M., and Kipnis, J. (2001). Protective autoimmunity: regulation and prospects for vaccination after brain and spinal cord injuries. Trends Mol. Med. 7, 252-258. (Pubitemid 32545521)
62. Stahel, P.F., and Barnum, S.R. (2006). The role of the complement system in CNS inflammatory diseases. Expert Rev. Clin. Immunol. 2, 445-456. (Pubitemid 44355575)
63. Stahel, P.F., Flierl, M.A., Morgan, B.P., Persigehl, I., Stoll, C., Conrad, C., Touban, B.M., Smith, W.R., Beauchamp, K., Schmidt, O.I., Ertel, W., and Leinhase, I. (2009). Absence of the complement regulatory molecule CD59a leads to exacerbated neuropathology after traumatic brain injury in mice. J. Neuroinflammation 6, 2.
64. Stahel, P.F., Morganti-Kossmann, M.C., and Kossmann, T. (1998). The role of the complement system in traumatic brain injury. Brain Res. Rev. 27, 243-256. (Pubitemid 28389310)
65. Stahel, P.F., Morganti-Kossmann, M.C., Perez, D., Redaelli, C., Gloor, B., Trentz, O., and Kossmann, T. (2001). Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury. J. Neurotrauma 18, 773-781. (Pubitemid 32769773)
66. Stahel, P.F., Shohami, E., Younis, F.M., Kariya, K., Otto, V.I., Lenzlinger, P.M., Grosjean, M.B., Eugster, H.P., Trentz, O., Kossmann, T., and Morganti-Kossmann, M.C. (2000). Experimental closed head injury: analysis of neurological outcome, blood-brain barrier dysfunction, intracranial neutrophil infiltration, and neuronal cell death in mice deficient in genes for pro-inflammatory cytokines. J. Cereb. Blood Flow Metab. 20, 369-380. (Pubitemid 30108456)
67. Szmydynger-Chodobska, J., Strazielle, N., Gandy, J.R., Keefe, T.H., Zink, B.J., Ghersi-Egea, J.F., and Chodobski, A. (2011). Posttraumatic invasion of monocytes across the bloodcerebrospinal fluid barrier. J. Cereb. Blood Flow Metab. [Aug 10; Epub ahead of print].
68. Toapanta, F.R., and Ross, T.M. (2006). Complement-mediated activation of the adaptive immune responses: role of C3d in linking the innate and adaptive immunity. Immunol. Res. 36, 197-210. (Pubitemid 46398596)
69. Van Beek, J., Elward, K., and Gasque, P. (2003). Activation of complement in the central nervous system: roles in neurodegeneration and neuroprotection. Ann. NY Acad. Sci. 992, 56-71. (Pubitemid 36706637)
70. Volanakis, J.E. (2002). The role of complement in innate and adaptive immunity. Curr. Top. Microbiol. Immunol. 266, 41-56. (Pubitemid 34297388)
71. Wise, P.M. (2002). Estrogens and neuroprotection. Trends Endocrinol. Metab. 13, 229-230. (Pubitemid 36733963)
72. Zhang, M., Michael, L.H., Grosjean, S.A., Kelly, R.A., Carroll, M.C., and Entman, M.L. (2006). The role of natural IgM in myocardial ischemia-reperfusion injury. J. Mol. Cell. Cardiol. 41, 62-67. (Pubitemid 43946958)