Abstract
We previously reported that murine experimental allergic encephalomyelitis can be induced by an additional intraperitoneal and intracerebral (i.c.) restimulation in resistant B6 mice after standard immunization with myelin antigens in complete Freund's adjuvant andBordetella pertussis coadjuvant. Neutrophils infiltrated into perivascular spaces at 12 h, followed by mononuclear cells 24 h after i.c. injection. In this study, we report that the i.c. injection induced the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). The kinetic expression of ICAM-1 or VCAM-1 on brain endothelial cells paralleled the infiltration of neutrophils and mononuclear cells, respectively. The infiltrated lymphocytes also expressed very late antigen-4 (VLA-4) molecules. The microvascular endothelial cells were positive for VCAM-1, whereas the surrounding mononuclear cells were VLA-4 positive. Furthermore, we found a unique subpopulation of cells with characteristics of CD4-CD8-Vβ8+ markers. The kinetic studies of this population showed that these cells were transiently depleted from 12 to 24 h after i.c. challenge (before the development of clinical symptoms) in cervical lymph nodes. These CD4-CD8-Vβ8+ cells can be expanded by in vitro culture with myelin basic protein or IL-2. No significant changes of CD4+/CD8+ cells were noted. CD4+CD8−CD3+ cells were also found in brain by double histochemical stains and were the major infiltrating cells at 24 or 48 h after i.c. challenge.
References
Acha-Orbea H, Steinman L, McDevitt HO. T cell receptors in murine autoimmune diseases. Ann Rev Immunol 7:371–405;1989.
Baron JL, Madri JA, Ruddle NH, Hashim G, Janeway CA. Surface expression of α4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med 177:56–78;1993.
Bendelac A, Killeen N, Littman DR, Schwartz RH. A subset of CD4+ thymocytes selected by MHC class I molecules. Science 263:1774–1778;1994.
Bradbury MW, Cserr HF. Drainage of cerebrospinal fluid and brain interstitial fluid into cervical lymphatics. In: Johnson MG, eds. Experimental Biology of the Lymphatic Circulation. New York, Elsevier, 355–394;1985.
Brown A, McFarlin DE, Raine CS. Chronologic neuropathology of relapsing experimental allergic encephalomyelitis in the mouse. Lab Invest 46:171–185;1982.
Chou FCH, Chou CHJ, Shapira R, Kibler RF. Basis of microheterogeneity of MBP. J Biol Chem 251:2671–2679;1976.
Claudio L, Raine CS, Brosnan CF. Evidence of persistent blood-brain barrier abnormalities in chronic-progressive multiple sclerosis. Acta Neuropathol 90:228–238;1995.
Crispe IN. CD4/CD8-negative T cells with αβ antigen receptors. Curr Opin Immunol 6:438–441;1994.
Cserr HF, Knopf PM. Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: A new view. Immunol Today 13:507–512;1992.
Cua JD, Hinton DR, Stohlman SA. Self-antigen-induced Th2 responses in experimental allergic encephalomyelitis (EAE)-resistant mice. Th2-mediated suppression of autoimmune disease. J Immunol 155:4052–4059;1995.
Erard F, Wild MT, Garcia-Sanz JA, Le Gros G. Switch of CD8 T cells to noncytolytic CD4−CD8− cells that make Th2 cytokines and help B cells. Science 260:1802–1805;1993.
Gordon LB, Kahn M, Cserr HF, Knopf PM. Comparison of serum antibody responses to CNS and systemically administered ovalbumin (OVA). Soc Neurosci Abstr 16:1209;1990.
Hafler DA, Weiner HL. MS: A CNS and systemic autoimmune disease. Immunol Today 10:104–107;1989.
Harling-Berg CJ, Knopf PM, Merian J, Cserr HF. Role of cervical lymph nodes in the systemic humoral response to human serum albumin microinfused into rat CSF. J Neuroimmunol 25:185–193;1989.
Harris JO, Frank JA, Patronas N, McFarlin DE, McFarland HF. Serial gadolinium-enhanced magnetic resonance imaging scans in patients with early, relapsing-remitting multiple sclerosis: Implications for clinical trials and natural history. Ann Neurol 29:548–555;1991.
Johnson RT, Hirsch RL, Griffin DE, Wolinsky JS, Roedenbeck S, de Soriano IL, Vaisberg A. Clinical and immunological studies of measles encephalitis. Trans Am Neurol Assoc 106:42–45;1981.
Liebert UG, Linington C, Meulen V. Induction of autoimmune reactions to myelin basic protein in measles virus encephalitis in Lewis rats. J Neuroimmunol 17:103–118;1988.
Matsuda M, Tsukada N, Miyagi K, Yanagisawa N. Adhesion of lymphocytes to endothelial cells in experimental allergic encephalomyelitis before and after treatment with endotoxin lipopolysaccharide. Int Arch Allergy Immunol 106:335–344;1995.
Mokhtarian F, McFarlin DE, Raine CS. Adoptive transfer of myelin basic protein-sensitized T cells produces chronic relapsing demyelinating disease in mice. Nature 309:356–358;1984.
Mukherjee A, Vogt RF, Linthicum DS. Measurement of myelin basic protein by radioimmunoassay in closed head trauma, multiple sclerosis and other neurological diseases. Clin Biochem 18:304–307;1985.
Paterson PY, Day ED. Current perspectives of neuroimmunologic disease: Multiple sclerosis and experimental allergic encephalomyelitis. Clin Immunol Rev 1:581–697;1981–1982.
Peterson PY, Swanborg RH. Demyelinating diseases of the central and peripheral nervous system. In: Samter M, ed. Immunological Disease, ed 4. Boston, Little Brown, 1877–1916;1988.
Pettinelli CB, McFarlin DE. Adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice after in vitro activation of lymph node cells by myelin basic protein: Requirement of Lyt 1+2- T lymphocytes. J Immunol 127:1420–1423;1981.
Raine CS. Biology of disease. Analysis of autoimmune demyelination: Its impact upon multiple sclerosis. Lab Invest 50:608–635;1984.
Reimann J. Double-negative (CD4−CD8−), TCRαβ-expressing, peripheral T cells. Scand J Immunol 34:679–688;1991.
Reimann J, Bellan A, Conrad P. Development of autoreactive L3T4+ T cells from double-negative (L3T4−/Ly-2−) Thy-1+ spleen cells of normal mice. Eur J Immunol 18:989–999;1988.
Seman M, Boudaly S, Roger T, Morisset J, Pham G. Autoreactive T cells in normal mice: Unrestricted recognition of self peptides on dendritic cell I-A molecules by CD4−CD8− T cell receptor α/β+ T cell clones expressing Vβ8.1 gene segments. Eur J Immunol 20:1265–1272;1990.
Shaw MK, Kim C, Ho KL, Lisak RP, Tse HY. A combination of adoptive transfer and antigenic challenge induces consistent murine experimental autoimmune encephalomyelitis in C57BL/6 mice and other reputed resistant strains. J Neuroimmunol 39:139–150;1992.
Steffen BJ, Butcher EC, Engelhardt B. Evidence for involvement of ICAM-1 and VCAM-1 in lymphocyte interaction with endothelium in experimental autoimmune encephalomyelitis in the central nervous system in SJL/J mouse. Am J Pathol 145:189–201;1994.
Swanborg RH. Experimental allergic encephalomyelitis. Methods Enzymol 162:413–421;1988.
de Talance A, Regnier D, Spinelli S, Morisset J, Seman M. Origin of autoreactive T helper cells. I. Characterization of Thy-1+, Lyt−, L3T4− precursors in the spleen of normal mice. J Immunol 137:1101–1108;1986.
Traugott U. Detailed analysis of early immunopathologic events during lesion formation in acute experimental autoimmune encephalomyelitis. Cell Immunol 119:114–129;1989.
Traugott U, Raine CS, McFarlin DE. Acute experimental allergic encephalomyelitis in the mouse: Immunopathology of the developing lesion. Cell Immunol 91:240–254;1985.
Tsai CY, Chow NH, Ho TS, Lei HY. Intracerebral injection of myelin basic protein (MBP) induces inflammation in brain and causes paraplegia in MBP-sensitized B6 mice. Clin Exp Immunol 109:(in press)1997.
Tuohy VK, Sobel RA, Lees MB. Myelin proteolipid protein-induced experimental allergic encephalomyelitis. Variation of disease expression in different strains of mice. J Immunol 140:1868–1873;1988.
Waksman BH, Reynolds WE. Multiple sclerosis as a disease of immune regulation. Proc Soc Exp Biol Med 175:282–294;1984.
Wang SD, Huang KJ, Lin YS, Lei HY. Sepsis-induced apoptosis of the thymocyte in mice. J Immunol 152:5014–5021;1994.
Wilcox CE, Ward AMV, Evans A, Baker D, Rothlein R, Turk JL. Endothelial cell expression of the intercellular adhesion molecule-1 (ICAM-1) in the central nervous system of guinea pig during acute and chronic relapsing experimental allergic encephalomyelitis. J Neuroimmunol 30:43–51;1990.
Yamada S, DePasquale M, Patlak SC, Cserr HF. Albumin outflow into deep cervical lymph from different regions of rabbit brain. Am J Physiol 261:H1197-H1204;1991.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ho, TS., Tsai, CY., Tsao, N. et al. Infiltrated cells in experimental allergic encephalomyelitis by additional intracerebral injection in myelin-basic-protein-sensitized B6 mice. J Biomed Sci 4, 300–307 (1997). https://doi.org/10.1007/BF02258354
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02258354