Interleukin-2

Interleukin-2 is an endogenous glycoprotein (cytokine), which is encoded by the interleukin-2 gene on the 4th chromosome. The synthesis of interleukin-2 occurs on the one hand after antigen stimulation, on the other hand specifically by interleukins-1 and interleukin-6, as well as non-specifically by lectins and vitamin E (alphaTocopherol).

Cells capable of interleukin-2 production are:

• NK cells
• transformed B lymphocytes
• leukemia cells and
• LAK cells.

Interleukin-2 is the major activating cytokine for T cells expressing CD4 antigen (T helper cells). In a broader sense, the cytokine thus acts as a growth and differentiation factor for T cells.

Interleukin-2 acts through different membrane-bound interleukin-2 receptors(CD121a) expressed by T lymphocytes. The density of these receptors is 500-5000/cell in the resting state of the cells, and 12,000/cell in the activated state.

3 different receptor types are expressed: high affinity, medium affinity and low affinity receptors. They are also called alpha/beta/gamma chains:

• the alpha chain(CD25), also called "T cell activation antigen", with low affinity
• the beta chain (CD122), also "interleukin-2Rbeta".
• the gamma chain (CD132), also "interleukin-2Rgamma".

These subunits are also parts of receptors of other cytokines.

The 3 receptor types are expressed separately but function together in different compositions as receptors with different affinities. The complex of alpha and gamma chains binds interleukin-2 with intermediate affinity; the high-affinity receptor is formed by a complex of all 3 chains (mainly by activated T cells and regulatory T cells).

In addition to membrane-bound IL-2 receptors, a soluble IL-2 receptor (sIL-2) circulating in plasma can also be detected. This is a fragment of a subunit. sIL-2R is increased in autoimmune diseases, infections, malignant myeloproliferative processes and other diseases of the immune system as well as after transplantation.

These different activities initiate 3 different intracellular signaling pathways: the MAP kinase pathway, the phosphoinositide-3-kinase (PI3K) pathway and the JAK-STAT pathway. Via this intracellular signaling cascade, peripheral blood T cells are differentiated into so-called lymphokine-activated killer (LAK) cells.

Activation of T lymphocytes leads to increased production of downstream cytokines (TNF, interferons). In addition to this "autocrine" co-directed T cell activation, interleukin-2 in B lymphocytes promotes the synthesis and secretion of immunoglobulins. Cyclosporin A and dexamethasone inhibit its synthesis in a dose-dependent manner.

Therapeutically, interleukin-2 was used with moderate success in the treatment of malignant (metastasized) tumors. Its functions can be inhibited therapeutically by blocking its receptor. The receptor antagonists basiliciximab and daclizumab are used for the prophylaxis of acute transplant rejection.

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