Perforin-positive Lymphozyten im peripheren Blut bei extrinsischem und intrinsischem Asthma[1] ^, [2]

Zusammenfassung:

Asthma bronchiale geht mit einer chronischen, T-Zell-vermittelten bronchialen Entzündung einher. Die Ursache der Erkrankung ist jedoch bis heute unklar. Ähnlich anderen T-Zell-vermittelten chronisch-entzündlichen Erkrankungen, die mit Autoimmunreaktionen assoziiert sind, gibt es auch einzelne Hinweise für Autoimmunphänomene beim Asthma. Da verschiedene Autoimmunerkrankungen mit der Expression von Perforin, einem zytotoxischen Molekül, das von Lymphozyten gebildet wird, einhergehen, sind wir der Hypothese nachgegangen, ob sich beim allergischen und intrinsischen Asthma vermehrt Perforin-produzierende Lymphozyten nachweisen lassen. Dazu wurde intrazellulär die Perforinexpression peripherer Blutlymphozyten von Patienten mit extrinsischem Asthma (n = 13), intrinsischen Asthma (n = 7) und gesunden Kontrollprobanden (n = 18) verglichen. Mittels Durchflusszytometrie wurden die Gesamtlymphozyten identifiziert und mit Hilfe monoklonaler Antikörper in ihre Subpopulationen CD3⁺, CD4⁺, CD8⁺, CD16⁺ und CD56⁺ unterteilt. Der Prozentsatz der Perforin-positiven Gesamtlymphozyten war, verglichen mit gesunden Kontrollprobanden, bei Patienten mit allergischem aber auch beim intrinsischem Asthma signifikant erhöht. Verglichen mit gesunden Kontrollprobanden ergab die Untersuchung der Lymphozytensubpopulationen signifikant höhere Prozentsätze an CD3-, CD4-, CD8- und CD56-positiven Zellen beim intrinsischen Asthma, die gleichzeitig auch Perforin exprimierten. Die Perforinexpression in CD4⁺-Zellen beim intrinsischen Asthma war sogar im Vergleich zum allergischen Asthma signifikant erhöht. Daraus ist zu schließen, dass das allergische und das intrinsische Asthma mit einem Anstieg der Perforin-Expression in T-Lymphozyten-Subpopulationen einhergehen.

Increase in Perforin-Positive Peripheral Blood Lymphocytes in Extrinsic and Intrinsic Asthma:

The cause of asthma, which has been linked to a chronic, T-cell-mediated bronchial inflammation, remains unclear. A number of other T-lymphocyte-mediated, chronic inflammatory disorders have been associated with autoimmunity and there are data indicating that autoimmune phenomena might also be present in asthma. Expression of perforin, a cytotoxic molecule produced by lymphocytes, has been implicated in the pathogenesis of autoimmune diseases. We therefore tested the hypothesis that allergic and intrinsic asthma might be associated with an increase in lymphocytes producing perforin by comparing the expression of intracellular perforin in peripheral blood lymphocytes of patients with extrinsic asthma (n = 13), intrinsic asthma (n = 7), and healthy control subjects (n = 18). Lymphocytes were identified using flow cytometry and subdivided into CD3(+), CD4(+), CD8(+), CD16(+), and CD56(+) subpopulations after staining with appropriate monoclonal antibodies. The percentage of perforin-positive total lymphocytes was significantly elevated in patients with allergic as well as intrinsic asthma when compared with normal control subjects. Analysis of lymphocyte subpopulations also revealed a significant increase in the percentage of CD3(+), CD4(+), CD8(+), and CD56(+) cells expressing perforin in allergic asthma and a significant increase in the percentage of CD4(+) and CD56(+) cells in intrinsic asthma when compared with healthy control subjects. Perforin expression in CD4(+) cells in intrinsic asthma was also significantly elevated compared with allergic asthma. We conclude that allergic and intrinsic asthma is associated with increased expression of perforin in T-lymphocyte subsets.

1 Deutsche Fassung von: Increase in Perforin-Positive Peripheral Blood Lymphocytes in Extrinsic and Intrinsic Asthma (Am J Respir Crit Care Med 2000; 161: 182 -186)

2 Herrn Prof. Dr. med. Heinrich Matthys zum 65. Geburtstag gewidmet

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1 Deutsche Fassung von: Increase in Perforin-Positive Peripheral Blood Lymphocytes in Extrinsic and Intrinsic Asthma (Am J Respir Crit Care Med 2000; 161: 182 -186)

2 Herrn Prof. Dr. med. Heinrich Matthys zum 65. Geburtstag gewidmet