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Stroke and T-cells

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Abstract

The microvasculature of the brain region affected by a stroke assumes an inflammatory phenotype that is characterized by endothelial cell activation and barrier dysfunction and the recruitment of adherent leukocytes. Although most attention has been devoted to the possible role of neutrophils in the tissue responses to ischemic stroke there is evidence that T-lymphocytes also accumulate in the postischemic brain. Although comparable detailed analyses of lymphocyte involvement in ischemic brain injury have not been performed, emerging findings suggest a role for T-cells in the pathogenesis of ischemic stroke. The recruitment of T-cells to the site of brain injury is critically dependent on the coordinated expression of adhesion molecules on the activated capillary endothelium. Whether the recruited lymphocytes are acting directly on brain tissue or indirectly through activation of other circulating blood cells and/or extravascular cells remain unclear. Cytotoxic CD8+ T-cells may induce brain injury through molecules released from their cytotoxic granules. CD4+ T-helper 1 (TH1) cells, which secrete proinflammatory cytokines, including interleukin-2 (IL-2), IL-12, interferon-γ, and tumor necrosis factor-α, may play a key role in the pathogenesis of stroke, whereas CD4+ TH2 cells may play a protective role through anti-inflammatory cytokines such as IL-4, IL-5, IL-10, and IL-13. T-cells should be considered as therapeutic targets for ischemic stroke. However, because infection is a leading cause of mortality in the postacute phase of ischemic stroke, and considering anti-inflammatory role of CD4+ TH2, treatment targeting T-cells should be carefully designed to reduce deleterious and enhance protective actions of T-cells.

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References

  • Aktas O., Smorodchenko A., Brocke S., et al. (2005) Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL. Neuron 46, 421–432.

    Article  PubMed  CAS  Google Scholar 

  • Arumugam T. V., Salter J. W., Chidlow, J. H., Ballantyne C. M., Kevil C. G., and Granger D. N. (2004) Contributions of LFA-1 and Mac-1 to brain injury and microvascular dysfunction induced by transient middle cerebral artery occlusion. Am. J. Physiol. Heart. Circ. Physiol. 287, H2555-H2560.

    Article  PubMed  CAS  Google Scholar 

  • Bachis A., Colangelo A. M., Vicini S., Doe P. P., De Bernardi M. A., Brooker G., and Mocchetti I. (2001) Interleukin-10 prevents glutamate-mediated cerebellar granule cell death by blocking caspase-3-like activity. J. Neurosci. 21, 3104–3112.

    PubMed  CAS  Google Scholar 

  • Barone F. C., Arvin B., White R. F., et al. (1997) Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 28, 1233–1244.

    PubMed  CAS  Google Scholar 

  • Battistini L., Piccio L., Rossi B., et al. (2003) CD8+ T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules: a critical role for P-selectin glycoprotein ligand-1. Blood 101, 4775–4782.

    Article  PubMed  CAS  Google Scholar 

  • Bochelen D., Rudin M., and Sauter A. (1999) Calcineurin inhibitors FK506 and SDZ ASM 981 alleviate the outcome of focal cerebral ischemic/reperfusion injury. J. Pharmacol. Exp. Ther. 288, 653–659.

    PubMed  CAS  Google Scholar 

  • Brecht S., Schwarze K., Waetzig V., et al. (2003) Changes in peptidyl-prolylcis/trans isomerase activity and FK506 binding protein expression following neuroprotection by FK506 in the ischemic rat brain. Neuroscience 120, 1037–1048.

    Article  PubMed  CAS  Google Scholar 

  • Bregenholt S. and Claesson M. H. (1998) Splenic Thelper cell type 1 cytokine profile and extramedullary haematopoiesis in severe combined immunodeficient (scid) mice with inflammatory bowel disease (IBD). Clin. Exp. Immunol. 111, 166–172.

    Article  PubMed  CAS  Google Scholar 

  • Buisson A., Lesne S., Docagne F., et al. (2003) Transforming growth factor-beta and ischemic brain injury. Cell Mol. Neurobiol. 23, 539–550.

    Article  PubMed  CAS  Google Scholar 

  • Burne-Taney M. J., Kofler J., Yokota N., Weisfeldt M., Traystman R. J., and Rabb H. (2003) Acute renal failure after whole body ischemia is characterized by inflammation and T cell-mediated injury. Am. J. Physiol. Renal Physiol. 285, F87-F94.

    PubMed  CAS  Google Scholar 

  • Burne-Taney M. J., Yokota-Ikeda N., and Rabb H. (2005) Effects of combined T- and B-cell deficiency on murine ischemia reperfusion injury. Am. J. Transplant. 5, 1186–1193.

    Article  PubMed  Google Scholar 

  • Butovsky O., Hauben E., and Schwartz M. (2001) Morphological aspects of spinal cord autoimmune neuroprotection: colocalization of T cells with B7—2 (CD86) and prevention of cyst formation. FASEB J. 15, 1065–1067.

    PubMed  CAS  Google Scholar 

  • Campanella M., Sciorati C., Tarozzo G., and Beltramo M. (2002) Flow cytometric analysis of inflammatory cells in ischemic rat brain. Stroke 33, 586–592.

    Article  PubMed  Google Scholar 

  • Carden D. L. and Granger D. N. (2000) Pathophysiology of ischaemia-reperfusion injury. J. Pathol. 190, 255–266.

    Article  PubMed  CAS  Google Scholar 

  • Chaparro-Huerta V., Rivera-Cervantes M. C., Flores-Soto M. E., Gomez-Pinedo U., and Beas-Zarate C. (2005) Proinflammatory cytokines and apoptosis following glutamate-induced excitotoxicity mediated by p38 MAPK in the hippocampus of neonatal rats. J. Neuroimmunol. 165, 53–62.

    Article  PubMed  CAS  Google Scholar 

  • Chavarria A. and Alcocer-Varela J. (2004) Is damage in central nervous system due to inflammation? Autoimmun. Rev. 3, 251–260.

    Article  PubMed  CAS  Google Scholar 

  • DeGraba T. J. (1998) The role of inflammation after acute stroke: utility of pursuing anti-adhesion molecule therapy. Neurology 51, S62-S68.

    PubMed  CAS  Google Scholar 

  • Dirnagl U., Simon R. P., and Hallenbeck J. M. (2003) Ischemic tolerance and endogenous neuroprotection. Trends Neurosci. 26, 248–254.

    Article  PubMed  CAS  Google Scholar 

  • Elneihoum A. M., Falke P., Axelsson L., Lundberg E., Lindgarde F., and Ohlsson K. (1996) Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases. Stroke 27, 1734–1738.

    PubMed  CAS  Google Scholar 

  • Enlimomab Acute Stroke Trial Investigators. (2001) Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology 57, 1428–1434.

    Google Scholar 

  • Fee D., Crumbaugh A., Jacques T., et al. (2003) Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury. J. Neuroimmunol. 136, 54–66.

    Article  PubMed  CAS  Google Scholar 

  • Flad H. D., Harter L., Petersen F., et al. (1997) Regulation of neutrophil activation by proteolytic processing of platelet-derived alpha-chemokines. Adv. Exp. Med. Biol. 421, 223–230.

    PubMed  CAS  Google Scholar 

  • Frijns C. J. and Kappelle L. J. (2002) Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke 33, 2115–2122.

    Article  PubMed  CAS  Google Scholar 

  • Furuya K., Takeda H., Azhar S., et al. (2001) Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study. Stroke 32, 2665–2674.

    PubMed  CAS  Google Scholar 

  • Garlichs C. D., Kozina S., Fateh-Moghadam S., et al. (2003) Upregulation of CD40-CD40 ligand (CD154) in patients with acute cerebral ischemia. Stroke 34, 1412–1418.

    Article  PubMed  CAS  Google Scholar 

  • Gary D. S., Bruce-Keller A. J., Kindy M. S., and Mattson M. P. (1998) Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor. J. Cereb. Blood Flow Metab. 18, 1283–1287.

    Article  PubMed  CAS  Google Scholar 

  • Gottlieb A., Krueger J. G., Bright R., et al. (2000) Effects of administration of a single dose of a humanized monoclonal antibody to CD11a on the immunobiology and clinical activity of psoriasis. J. Am. Acad. Dermatol. 42, 428–435.

    Article  PubMed  CAS  Google Scholar 

  • Groux H. and Powrie F. (1999) Regulatory T cells and inflammatory bowel disease. Immunol. Today 20, 442–445.

    Article  PubMed  CAS  Google Scholar 

  • Grutz G. (2005) New insights into the molecular mechanism of interleukin-10-mediated immunosuppression. J. Leukoc. Biol. 77, 3–15.

    PubMed  Google Scholar 

  • Guo Z., Iyun T., Fu W., Zhang P., and Mattson M. P. (2004) Bone marrow transplantation reveals roles for brain macrophage/microglia TNF signaling and nitric oxide production in excitotoxic neuronal death. Neuromol. Med. 5, 219–234.

    Article  CAS  Google Scholar 

  • Han H. S. and Yenari M. A. (2003) Cellular targets of brain inflammation in stroke. Curr. Opin. Investig. Drugs 4, 522–529.

    PubMed  CAS  Google Scholar 

  • Hauben E., Butovsky O., Nevo U., et al. (2000) Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J. Neurosci. 20, 6421–6430.

    PubMed  CAS  Google Scholar 

  • Henrich-Noack P., Prehn J. H., and Krieglstein J. (1996) TGF-beta 1 protects hippocampal neurons against degeneration caused by transient global ischemia. Dose-response relationship and potential neuroprotective mechanisms. Stroke 27, 1609–1614.

    PubMed  CAS  Google Scholar 

  • Hickey W. F. and Kimura H. (1988) Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239, 290–292.

    Article  PubMed  CAS  Google Scholar 

  • Hogg N., Smith A., McDowall A., Giles K., Stanley P., Laschinger M., and Henderson R. (2004) How T cells use LFA-1 to attach and migrate. Immunol. Lett. 92, 51–54.

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa M., Cooper D., Arumugam T. V., Zhang J. H., Nanda A., and Granger D. N. (2004a) Platelet-leukocyte-endothelial cell interactions after middle cerebral artery occlusion and reperfusion. J. Cereb. Blood Flow Metab. 24, 907–915.

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa M., Cooper D., Russell J., Salter J. W., Zhang J. H., Nanda A., and Granger D. N. (2003) Molecular determinants of the prothrombogenic and inflammatory phenotype assumed by the postischemic cerebral microcirculation. Stroke 34, 1777–1782.

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa M., Vowinkel T., Stokes K. Y., Arumugam T. V., Yilmaz G., Nanda A., and Granger D. N. (2005) CD40/CD40 ligand signaling in mouse cerebral microvasculature after focal ischemia/reperfusion. Circulation 111, 1690–1696.

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa M., Zhang J. H., Nanda A., and Granger D. N. (2004b) Inflammatory responses to ischemia and reperfusion in the cerebral microcirculation. Front. Biosci. 9, 1339–1347.

    Article  PubMed  CAS  Google Scholar 

  • Jander S., Kraemer M., Schroeter M., Witte O. W., and Stoll G. (1995) Lymphocytic infiltration and expression of intercellular adhesion molecule-1 in photochemically induced ischemia of the rat cortex. J. Cereb. Blood Flow Metab. 15, 42–51.

    PubMed  CAS  Google Scholar 

  • Kapadia S. R., Spero D. M., and Eriksson M. (2001) An improved synthesis of chiral alpha-(4-bromobenzyl)alanine ethyl ester and its application to the synthesis of LFA-1 antagonist BIRT-377. J. Org. Chem. 66, 1903–1905.

    Article  PubMed  CAS  Google Scholar 

  • Kim E. S., Kim R. S., Ren R. F., Hawver D. B., and Flanders K. C. (1998) Transforming growth factor-beta inhibits apoptosis induced by beta-amyloid peptide fragment 25–35 in cultured neuronal cells. Brain Res. Mol. Brain Res. 62, 122–130.

    Article  PubMed  CAS  Google Scholar 

  • Kim J. S., Chopp M., Chen H., Levine S. R., Carey J. L., and Welch K. M. (1995) Adhesive glycoproteins CD11a and CD18 are upregulated in the leukocytes from patients with ischemic stroke and transient ischemic attacks. J. Neurol. Sci. 128, 45–50.

    Article  PubMed  CAS  Google Scholar 

  • Kipnis J., Yoles E., Porat Z., et al. (2000) T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: possible therapy for optic neuropathies. Proc. Natl. Acad. Sci. USA 97, 7446–7451.

    Article  PubMed  CAS  Google Scholar 

  • Kostulas N., Pelidou S. H., Kivisakk P., Kostulas V., and Link H. (1999) Increased IL-1beta, IL-8, and IL-17 mRNA expression in blood mononuclear cells observed in a prospective ischemic stroke study. Stroke 30, 2174–2179.

    PubMed  CAS  Google Scholar 

  • Kubes P. and Ward P. A. (2000) Leukocyte recruitment and the acute inflammatory response. Brain Pathol. 10, 127–135.

    Article  PubMed  CAS  Google Scholar 

  • Kuchroo V. K., Greer J. M., Kaul D., et al. (1994) A single TCR antagonist peptide inhibits experimental allergic encephalomyelitis mediated by a diverse T cell repertoire. J. Immunol. 153, 3326–3336.

    PubMed  CAS  Google Scholar 

  • Le Moine O., Louis H., Demols A., et al. (2000) Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice. Hepatology 31, 1266–1274.

    Article  PubMed  Google Scholar 

  • Liu T., Clark R. K., McDonnell P. C., Young P. R., White R. F., Barone F. C., and Feuerstein G. Z. (1994) Tumor necrosis factor-alpha expression in ischemic neurons. Stroke 25, 1481–1488.

    PubMed  CAS  Google Scholar 

  • Liu T., McDonnell P. C., Young P. R., et al. (1993) Interleukin-1 beta mRNA expression in ischemic rat cortex. Stroke 24, 1746–1750.

    PubMed  CAS  Google Scholar 

  • Matsuo Y., Onodera H., Shiga Y., et al. (1994) Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat. Brain Res. 656, 344–352.

    Article  PubMed  CAS  Google Scholar 

  • Mattson M. P., Goodman Y., Luo H., Fu W., and Furukawa K. (1997) Activation of NF-kappa B protects hippocampal neurons against oxidative stress-induced apoptosis: evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration. J. Neurosci. Res. 49, 681–697.

    Article  PubMed  CAS  Google Scholar 

  • McLaurin J., D’Souza S., Stewart J., et al. (1995) Effect of tumor necrosis factor alpha and beta on human oligodendrocytes and neurons in culture. Int. J. Dev. Neurosci. 13, 369–381.

    Article  PubMed  CAS  Google Scholar 

  • McNeill H., Williams C., Guan J., et al. (1994) Neuronal rescue with transforming growth factor-beta 1 after hypoxic-ischaemic brain injury. Neuroreport 5, 901–904.

    Article  PubMed  CAS  Google Scholar 

  • Meucci O. and Miller R. J. (1996) gp120-induced neurotoxicity in hippocampal pyramidal neuron cultures: protective action of TGF-beta1. J. Neurosci. 16, 4080–4088.

    PubMed  CAS  Google Scholar 

  • Moalem G., Leibowitz-Amit R., Yoles E., Mor F., Cohen I. R., and Schwartz M. (1999) Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat. Med. 5, 49–55.

    Article  PubMed  CAS  Google Scholar 

  • Mosmann T. R. and Sad S. (1996) The expanding universe of T-cell subsets: Th1, TH2 and more. Immunol. Today 17, 138–146.

    Article  PubMed  CAS  Google Scholar 

  • Mulcahy N. J., Ross J., Rothwell N. J., and Loddick S. A. (2003) Delayed administration of interleukin-1 receptor antagonist protects against transient cerebral ischaemia in the rat. Br. J. Pharmacol. 140, 471–476.

    Article  PubMed  CAS  Google Scholar 

  • Nawashiro H., Martin D., and Hallenbeck J. M. (1997) Inhibition of tumor necrosis factor and amelioration of brain infarction in mice. J. Cereb. Blood Flow Metab. 17, 229–232.

    Article  PubMed  CAS  Google Scholar 

  • Neumann H., Cavalie A., Jenne D. E., and Wekerle H. (1995) Induction of MHC class I genes in neurons. Science 269, 549–552.

    Article  PubMed  CAS  Google Scholar 

  • Neumann H., Medana I. M., Bauer J., and Lassmann H. (2002) Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases. Trends Neurosci. 25, 313–319.

    Article  PubMed  CAS  Google Scholar 

  • Neumann H., Schmidt H., Cavalie A., Jenne D., and Wekerle H. (1997) Major histocompatibility complex (MHC) class I gene expression in single neurons of the central nervous system: differential regulation by interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. J. Exp. Med. 185, 305–316.

    Article  PubMed  CAS  Google Scholar 

  • O’Garra A., Vieira P. L., Vieira P., and Goldfeld A. E. (2004) IL-10-producing and naturally occurring CD4+ Tregs: limiting collateral damage. J. Clin. Invest. 114, 1372–1378.

    Article  PubMed  CAS  Google Scholar 

  • Omari K. M. and Dorovini-Zis K. (2003) CD40 expressed by human brain endothelial cells regulates CD4+ T cell adhesion to endothelium. J. Neuroimmunol. 134, 166–178.

    Article  PubMed  CAS  Google Scholar 

  • Phillis J. W., Diaz F. G., O’Regan M. H., and Pilitsis J. G. (2002) Effects of immunosuppressants, calcineurin inhibition, and blockade of endoplasmic reticulum calcium channels on free fatty acid efflux from the ischemic/reperfused rat cerebral cortex. Brain Res. 957, 12–24.

    Article  PubMed  CAS  Google Scholar 

  • Piccio L., Rossi B., Scarpini E., et al. (2002) Molecular mechanisms involved in lymphocyte recruitment in inflamed brain microvessels: critical roles for P-selectin glycoprotein ligand-1 and heterotrimeric G(i)-linked receptors. J. Immunol. 168, 1940–1949.

    PubMed  CAS  Google Scholar 

  • Prehn J. H., Bindokas V. P., Marcuccilli C. J., Krajewski S., Reed J. C., and Miller R. J. (1994) Regulation of neuronal Bcl2 protein expression and calcium homeostasis by transforming growth factor type beta confers wide-ranging protection on rat hippocampal neurons. Proc. Natl. Acad. Sci. USA 91, 12,599–12,603.

    Article  CAS  Google Scholar 

  • Prehn J. H. and Krieglstein J. (1994) Opposing effects of transforming growth factor-beta 1 on glutamate neurotoxicity. Neuroscience 60, 7–10.

    Article  PubMed  CAS  Google Scholar 

  • Prehn J. H., Peruche B., Unsicker K., and Krieglstein J. (1993) Isoform-specific effects of transforming growth factors-beta on degeneration of primary neuronal cultures induced by cytotoxic hypoxia or glutamate. J. Neurochem. 60, 1665–1672.

    Article  PubMed  CAS  Google Scholar 

  • Prestigiacomo C. J., Kim S. C., Connolly E. S., Jr., Liao H., Yan S. F., and Pinsky D. J. (1999) CD18-mediated neutrophil recruitment contributes to the pathogenesis of reperfused but not nonreperfused stroke. Stroke 30, 1110–1117.

    PubMed  CAS  Google Scholar 

  • Price C. J., Warburton E. A., and Menon D. K. (2003) Human cellular inflammation in the pathology of acute cerebral ischaemia. J. Neurol. Neurosurg. Psychiatry 74, 1476–1484.

    Article  PubMed  CAS  Google Scholar 

  • Ruocco A., Nicole O., Docagne F., et al. (1999) A transforming growth factor-beta antagonist unmasks the neuroprotective role of this endogenous cytokine in excitotoxic and ischemic brain injury. J. Cereb. Blood Flow Metab. 19, 1345–1353.

    Article  PubMed  CAS  Google Scholar 

  • Schielke G. P., Yang G. Y., Shivers B. D., and Betz A. L. (1998) Reduced ischemic brain injury in interleukin-1 beta converting enzyme-deficient mice. J. Cereb. Blood Flow Metab. 18, 180–185.

    Article  PubMed  CAS  Google Scholar 

  • Schroeter M., Jander S., Witte O. W., and Stoll G. (1994) Local immune responses in the rat cerebral cortex after middle cerebral artery occlusion. J. Neuroimmunol. 55, 195–203.

    Article  PubMed  CAS  Google Scholar 

  • Schwartz M. and Hauben E. (2002) T cell-based therapeutic vaccination for spinal cord injury. Prog. Brain Res. 137, 401–406.

    PubMed  Google Scholar 

  • Segal B. M. (2003) Experimental autoimmune encephalomyelitis: cytokines, effector T cells, and antigen-presenting cells in a prototypical Th1-mediated autoimmune disease. Curr. Allergy Asthma Rep. 3, 86–93.

    Article  PubMed  Google Scholar 

  • Shigematsu T., Wolf R. E., and Granger D. N. (2002) T-lymphocytes modulate the microvascular and inflammatory responses to intestinal ischemia-reperfusion. Microcirculation 9, 99–109.

    Article  PubMed  Google Scholar 

  • Soriano S. G., Coxon A., Wang Y. F., et al. (1999) Mice deficient in Mac-1 (CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury. Stroke 30, 134–139.

    PubMed  CAS  Google Scholar 

  • Stevens S. L., Bao J., Hollis J., Lessov N. S., Clark W. M., and Stenzel-Poore M. P. (2002) The use of flow cytometry to evaluate temporal changes in inflammatory cells following focal cerebral ischemia in mice. Brain Res. 932, 110–119.

    Article  PubMed  CAS  Google Scholar 

  • Stoll G., Muller S., Schmidt B., van der Meide P., Jung S., Toyka K. V., and Hartung H. P. (1993) Localization of interferon-gamma and Ia-antigen in T cell line-mediated experimental autoimmune encephalomyelitis. Am. J. Pathol. 142, 1866–1875.

    PubMed  CAS  Google Scholar 

  • Tailor A. and Granger D. N. (2000) Role of adhesion molecules in vascular regulation and damage. Curr. Hypertens Rep. 2, 78–83.

    Article  PubMed  CAS  Google Scholar 

  • Toda M., Totsuka M., Furukawa S., et al. (2000) Down-regulation of antigen-specific antibody production by TCR antagonist peptides in vivo. Eur. J. Immunol. 30, 403–414.

    Article  PubMed  CAS  Google Scholar 

  • Traugott U. (1987) Multiple sclerosis: relevance of class I and class II MHC-expressing cells to lesion development. J. Neuroimmunol. 16, 283–302.

    Article  PubMed  CAS  Google Scholar 

  • van Exel E., Gussekloo J., de Craen A. J., Bootsma-van der Wiel A., Frolich M., and Westendorp R. G. (2002) Inflammation and stroke: the Leiden 85-Plus Study. Stroke 33, 1135–1138.

    Article  PubMed  Google Scholar 

  • Vandendries E. R., Furie B. C., and Furie B. (2004) Role of P-selectin and PSGL-1 in coagulation and thrombosis. Thromb. Haemost. 92, 459–466.

    PubMed  CAS  Google Scholar 

  • Vass K. and Lassmann H. (1990) Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system. Am. J. Pathol. 137, 789–800.

    PubMed  CAS  Google Scholar 

  • Vemuganti R., Dempsey R. J., and Bowen K. K. (2004) Inhibition of intercellular adhesion molecule-1 protein expression by antisense oligonucleotides is neuroprotective after transient middle cerebral artery occlusion in rat. Stroke 35, 179–184.

    Article  PubMed  CAS  Google Scholar 

  • Vila N., Castillo J., Davalos A., Esteve A., Planas A. M., and Chamorro A. (2003) Levels of anti-inflammatory cytokines and neurological worsening in acute ischemic stroke. Stroke 34, 671–675.

    Article  PubMed  CAS  Google Scholar 

  • Wang X., Feuerstein G. Z., Xu L., et al. (2004) Inhibition of tumor necrosis factor-alpha-converting enzyme by a selective antagonist protects brain from focal ischemic injury in rats. Mol. Pharmacol. 65, 890–896.

    Article  PubMed  CAS  Google Scholar 

  • Wang X., Li X., Schmidt D. B., et al. (2000) Identification and molecular characterization of rat CXCR3: receptor expression and interferon-inducible protein-10 binding are increased in focal stroke. Mol. Pharmacol. 57, 1190–1198.

    PubMed  CAS  Google Scholar 

  • Ward P. A., Warren J. S., and Johnson K. J. (1988) Oxygen radicals, inflammation, and tissue injury. Free Radic. Biol. Med. 5, 403–408.

    Article  PubMed  CAS  Google Scholar 

  • Werther W. A., Gonzalez T. N., O’Connor S. J., et al. (1996) Humanization of an anti-lymphocyte function-associated antigen (LFA)-1 monoclonal antibody and reengineering of the humanized antibody for binding to rhesus LFA-1. J. Immunol. 157, 4986–4995.

    PubMed  CAS  Google Scholar 

  • Whatley R. E., Zimmerman G. A., McIntyre T. M., and Prescott S. M. (1990) Lipid metabolismand signal transduction in endothelial cells. Prog. Lipid Res. 29, 45–63.

    Article  PubMed  CAS  Google Scholar 

  • Williams C. B., Vidal K., Donermeyer D., Peterson D. A., White J. M., and Allen P. M. (1998) In vivo expression of a TCR antagonist: T cells escape central tolerance but are antagonized in the periphery. J. Immunol. 161, 128–137.

    PubMed  CAS  Google Scholar 

  • Yenari M. A., Kunis D., Sun G. H., et al. (1998) Hu23F2G, an antibody recognizing the leukocyte CD11/CD18 integrin, reduces injury in a rabbit model of transient focal cerebral ischemia. Exp. Neurol. 153, 223–233.

    Article  PubMed  CAS  Google Scholar 

  • Yoshimura A., Mori H., Ohishi M., Aki D., and Hanada T. (2003) Negative regulation of cytokine signaling influences inflammation. Curr. Opin. Immunol. 15, 704–708.

    Article  PubMed  CAS  Google Scholar 

  • Ysebaert D. K., De Greef K. E., De Beuf A., et al. (2004) T cells as mediators in renal ischemia/reperfusion injury. Kidney Int. 66, 491–496.

    Article  PubMed  CAS  Google Scholar 

  • Zhu Y., Culmsee C., Klumpp S., and Krieglstein J. (2004) Neuroprotection by transforming growth factor-beta1 involves activation of nuclear factor-kappaB through phosphatidylinositol-3-OH kinase/Akt and mitogen-activated protein kinase-extracellular-signal regulated kinase1,2 signaling pathways. Neuroscience 123, 897–906.

    Article  PubMed  CAS  Google Scholar 

  • Zwacka R. M., Zhang Y., Halldorson J., Schlossberg H., Dudus L., and Engelhardt J. F. (1997) CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver. J. Clin. Invest. 100, 279–289.

    Article  PubMed  CAS  Google Scholar 

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  1. Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, 21224, Baltimore, MD

    Thiruma V. Arumugam & Mark P. Mattson

  2. Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 71130, Shreveport, LA

    D. Neil Granger

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  1. Thiruma V. Arumugam
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Correspondence to Thiruma V. Arumugam.

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Arumugam, T.V., Granger, D.N. & Mattson, M.P. Stroke and T-cells. Neuromol Med 7, 229–242 (2005). https://doi.org/10.1385/NMM:7:3:229

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