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Die Rolle von Interleukin-2 bei der Aktivierung von zytotoxischen T-Lymphozyten

The role of Interleukin-2 during the activation of cytotoxic T-lymphocytes

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Summary

This review describes our present information on the interactions of cellular and humoral components involved in the induction of cytotoxic T-lymphocyte (CTL) responses. Since soluble, hormone-like growth factors (interleukins) are intimately involved in such reactions, the discussion will focus on the role of such mediators, in particular on the functional role of Interleukin-2 (1–2).

Il-2 is a soluble, non-antigen-specific glycoprotein with a molecular weight of 15,000 daltons (human Il-2) or 30,000 daltons (murine Il-2). Il-2 is derived from T-helper-lymphocytes, that bear in the mouse the Lyt 1-cell surface marker and in the human the OKT4 phenotype. In order to produce Il-2, T-helperlymphocytes require two distinct signals that are delivered by antigen-presenting cells (macrophages): Signal 1 is the antigen as presented by macrophages, signal 2 represents the soluble macrophage product, Interleukin-1 (Il-1). Il-2 in turn controls the antigen-independent clonal expansion of all T cells that bear receptors for Il-2. The most prominent target cells for Il-2 are the CTL precursors, known to be in the mouse Lyt 123*-positive or OKT8-positive in humans. “Resting”, naive T cells do not express Il-2-receptors. However, following antigen binding of antigen (antigen-receptor interaction), the respective clones will express the Il-2 receptor. Il-2 driven proliferation of the “activated” clones is completely dependent on the bio-availability of Il-2.

Our present knowledge on the function of Il-2, and the possibilities to manipulate experimentally either the Il-2 production by T helper cells, or the Il-2 responsiveness of CTL-precursors, point to new strategies both in diagnostic and in therapy of immune defects that can be the result, in vivo, of either a lack or a surplus of Il-2.

Zusammenfassung

Der vorliegende Artikel stellt eine Übersicht dar Über die derzeitigen Vorstellungen des Zusammenwirkens zellulärer und humoraler Faktoren, die zu T-Zell-vermittelten zytotoxischen Immunreaktionen führen. Da im Ablauf derartiger Immunreaktionen hormonähnliche Wachstumsfaktoren (interleukine) eine entscheidende Rolle spielen, liegt der Schwerpunkt der Diskussion auf der Beschreibung dieser Mediatoren; insbesondere wird die Bedeutung von Interleukin-2 (Il-2) diskutiert.

Il-2 ist ein lösliches, nicht antigenspezifisches Glykoprotein mit einem Molekulargewicht von 15 000 Dalton (humanes Il-2) bzw. 30 000 Dalton (murines Il-2). Es wird in vitro von T-Helfer-Lymphozyten sezerniert, die in der Maus den Lyt 1 Oberflächen-Phänotyp aufweisen und beim Menschen OKT4-positiv sind. Die Aktivierung der T-Helfer-Lymphozyten zur Il-2-Produktion erfordert zwei Kommunikationssignale, die durch Antigen-präsentierende Zellen (Makrophagen) bereitgestellt werden: Signal 1 ist das durch Makrophagen präsentierte Antigen; Signal 2 stellt das lösliche Makrophagen-Produkt Interleukin-1 (Il-1) dar.

Dic biologische Wirkung von Il-2 besteht in der Antigen-unabhängigen klonalen Expansion all jener T-Zellen, die einen Rezeptor für Il-2 besitzen. Solche Zellen sind vor allem die Vorläuferzellen von zytotoxischen T-Lymphozyten (ZTL-V), die in der Maus den Lyt 123*-und beim Menschen den OKT8-positiven Oberflächen-Phänotyp aufweisen. „Ruhende“, naive T-Zellen exprimieren keinen Rezeptor für Il-2. Erst nach Antigen-Bindung (Rezeptor-Antigen Interaktion) entwickeln T-Zellen einen Il-2-Rezeptor; sie sind nun empfindlich für das durch Interleukin-2 vermittelte Mitogen-Signal. Die danach einsetzende Proliferation der „aktivierten“ T-Zell-Klone ist nur noch abhängig von der Bioverfügbarkeit von Il-2. Die derzeitigen Kenntnisse über die Eigenschaften von Il-2 und die experimentelle Manipulation der Il-2-Produktion durch T-Helfer-Zellen bzw. der Il-2-Empfindlichkeit versprechen neue Ansätze bei der Diagnostik und möglicherweise bei der Therapie von Immundefekten, die in vivo sowohl durch einen Mangel als auch durch einen Überschuß an Il-2 verursacht sein können.

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  1. Institut für Medizinische Mikrobiologie der Johannes Gutenberg-Universität Mainz, Germany

    Werner Solbach, Martin Röllinghoff & Hermann Wagner

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Solbach, W., Röllinghoff, M. & Wagner, H. Die Rolle von Interleukin-2 bei der Aktivierung von zytotoxischen T-Lymphozyten. Klin Wochenschr 61, 67–75 (1983). https://doi.org/10.1007/BF01496657

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