Abstract
Cell-mediated cytotoxicity is thought to play an important role in the immunopathogenesis of inflammatory myopathies. We determined whether lymphocytes circulating in patient peripheral blood contain automyocytotoxic precursors. Peripheral blood mononuclear cells, sheep red blood cell rosetting (E+) and nonrosetting (E−) cells, were isolated from patients with polymyositis or dermatomyositis and tested for their ability to kill autologous-cultured myotubes derived from diseased muscle biopsies. Patient-derived as well as normal allogeneic mononuclear cells lysed both polymyositis–dermatomyositis and nonrelated myotubes. However, whereas patient E+ cells were preferentially cytotoxic to autologous myotubes, their E− cells did not discriminate autologous from allogeneic targets. Furthermore, cultures of patient E+ cells triggered by phytohemagglutinin and interleukin-2 maintained myocytotoxic potential. In these cultures, virtually all autologous but only 50% of allogeneic killing was mediated by CD3+ T cells. Moreover, autologous cell-mediated killing was abrogated by anti-CD3 monoclonal antibodies. In conclusion, both myocytotoxic CD3+ T-cell clones specific for autologous myotubes, as well as non-T cells, which are nonspecifically myocytotoxic, are present in the peripheral blood of patients with inflammatory myopathies.
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REFERENCES
Arahata K, Engel AG: Monoclonal antibody analysis of mononuclear cells in myopathies. II: phenotype of autoinvasive and inclusion body myositis. Ann Neurol 16:209–215, 1984
Arahata K, Engel AG: Monoclonal antibody analysis of mononuclear cells in myopathies. V: Identification and quantitation of T8+ cytotoxic and T8+ suppressor cells. Ann Neurol 23:493–499, 1988
Engel AG, Arahata K: Mononuclear cells in myopathies: quantitation of functionally distinct subsets, recognition of antigenspecific cell–mediated cytotoxicity in some diseases, and implications for the pathogenesis of the different inflammatory myopathies. Hum Pathol 17:704–721, 1986
Emslie–Smith AM, Aragata K, Engel AG: Major Histocompatibility complex class I antigen expression, immunolocalization of interferon subtypes, and T cell mediated cytotoxicity in myopathies. Hum Pathol 20:224–231, 1989
Hohlfeld R, Engel AG: Coculture with autologous myotubes of cytotoxic T–cells isolated from muscle in inflammatory myopathies. Ann Neurol 29:498–507, 1991
Dawkins RL, Mastaglia FL: Cell mediated cytotoxicity to muscle in PM: effect of immunosuppression. N Engl J Med 288:434–438, 1973
Haas DC, Arnason BGW: Cell–mediated immunity in PM: Creatinine phosphokinase release from muscle cultures. Arch Neurol 31:192–196, 1974
Kakulas BA., Shute GH., Keclerc ALF: In vitro destruction of human foetal muscle cultures by peripheral blood lymphocytes from patients with PM and lupus erythematosus. Proc Aust Assoc Neurol 8:85–92, 1971
Haas DC: Absence of cell–mediated cytotoxicity to muscle cultures in PM. J Rheumatol 7:671–676, 1980
Rosenschein U, Radnay D, Shoham J, et al: Human muscle derived, tissue specific, myocoytotoxic T cell lines in DM. Clin Exp Immunol 67:309–318, 1987
Targoff IN, Miller FW, Medsger TA Jr, Oddis CV: Classification criteria for the idiopathic inflammatory myopathies. Curr Opin Rheumatol 9:527–535, 1997
Miranda AF, Bonilla E, Martucci G, Moraes CT, Hays AP, Dimauro S: Immunocytochemical study of dystrophin in muscle cultures from patients with Duchenne muscular dystrophy and unaffected control patients. Am J Pathol. 132:410–416, 1988
Bank I, Chess L: Perturbation of the T4 molecule transmits a negative signal to T cells. J Exp Med 162:1294–1303, 1985
Bank I, dePinho RA, Brenner MB, Cassimeris J, Alt F, Chess L: A novel heterodimer on the surface of immature thymocytes. Nature 322:179–181, 1986
Lindberg C, Oldfors A, Tarkowski A: Restricted use of T cell receptor V genes in endomysial infiltrates of patients with inflammatory myopathies. Eur J Immunol 24:2659–2663, 1994
Bender A, Ernst N, Iglesias A, Dornmair K, Wekerle H, Hohlfeld R: T cell receptor repertoire in polymyositis: Clonal expansion of autoaggressive CD8+ T cells. J Exp Med 181:1863–1868, 1995
Nagaraju K, Raben N, Villalba ML, Danning C, Loeffler LA, Lee E, Tresser N, Abati A, Fetsch P, Plotz PH: Costimulatory markers in muscle of patients with idiopathic inflammatory mýopathies and in cultured muscle cells. Clin Immunol 92:161–169, 1999
Hohlfeld R, Engel AG: Lysis of myotubes by alloreactive cytotoxic T–cells and natural killer cells: Relevance to myoblast transplantation. J Clin Invest 86:370–374, 1990
Sugiura T, Murakawa Y, Nagai A, Kondo M, Kobayashi S: Fas and Fas ligand interaction induces apoptosis in inflammatory myopathies: CD4+ T–cells cause muscle cell injury directly in PM. Arthritis Rheum 42:291–298, 1999
Behrens L, Bender A, Johnson MA, Hohlfeld R: Cytotoxic mechanisms in inflammatory myopathies. Co–expression of Fas and protective Bcl–2 in muscle fibres and inflammatory cells. Brain 120:929–938, 1997
Moretta L, Biassoni R, Bottino C, Mingari MC, Moretta A: Human NK–cell receptors. Immunol Today 21:420–422, 2000
Khakoo SI, Rajalingam R, Shum BP, Weidenbach K, Flodin L, Muir DG, Canavez F, Cooper SL, Valiante NM, Lanier LL, Parham P: Rapid evolution of NK cell receptor systems demonstrated by comparison of chimpanzees and humans. Immunity 12:687–698, 2000
Matsuda JL, Naidenko OV, Gapin L, Nakayama T, Taniguchi M, Wang CR, Koezuka Y, Kronenberg M: Tracking the response of natural killer T cells to a glycolipid antigen using CDId tetramers. J Exp Med 192:741–754, 2000
Smith KA: Interleukin–2: Inception, impact and implications. Science 240:1169–1176, 1988.
Dalakas MC: Immunopathogenesis of inflammatory myopathies. Ann Neurol 37:S74–86, 1995
De Rossi M, Bernasconi P, Baggi F, de Waal Malefyt R, Mantegazza R: Cytokines and chemokines are both expressed by human myoblasts: Possible relevance for the immune pathogenesis of muscle inflammation. Int Immunol 12:1329–1335, 2000
Sugiura T, Kawaguchi Y, Harigai M, Takagi K, Ohta S, Fukasawa C, Hara M, Kamatani N: Increased CD40 expression on muscle cells of polymyositis and dermatomyositis: Role of CD40–CD40 ligand interaction in IL–6, IL–8, IL–15, and monocyte chemoattractant protein–1 production. J Immunol 164:6593–6600, 2000
Tam PE, Schmidt AM, Ytterberg SR, Messner RP: Duration of virus persistence and its relationship to inflammation in the chronic phase of coxsackievirus B1–induced murine PM. J Lab Clin Med 123:346–356, 1994
Carota A, Pizzolato GP, Redard M, Gailloud P, Grau GE: Adhesion molecules in HIV–related and idiopathic PM: immunohistochemical studies. Clin Neuropathol 16:312–318, 1997
Wolf RE, Baethge BA: Interleukin–1 alpha, interleukin–2, and soluble interleukin–2 receptors in PM. Arthritis Rheum 33:1007–1014, 1990
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Bank, I., Miranda, A.F. & Chess, L. Mechanisms of Cell-Mediated Myocytotoxicity in the Peripheral Blood of Patients with Inflammatory Myopathies. J Clin Immunol 21, 328–334 (2001). https://doi.org/10.1023/A:1012236618892
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DOI: https://doi.org/10.1023/A:1012236618892