Targets of the stimulatory activity of IL2

Most cells of the immune system can express the high-affinity (IL-2Ra, (3, y) or the intermediate-affinity (lL-2R|3y) IL-2 receptors, either spontaneously or after stimulation. Consequently IL-2 has many targets (Figure 2).

T lymphocytes

The primary role of IL-2 is to expand activated CD4 and CD8 lymphocytes. On TU1 cells IL-2 acts in an autocrine fashion. IL-2 also induces the growth of Th2 and CD8 lymphocytes as a paracrine factor. IL-2 has no influence on the Th1/Th2 balance. On CD8 lymphocytes IL-2 stimulates cytotoxic activity. After stimulation T lymphocytes produce many cytokines and express the corresponding receptors. However IL-2 remains the main cytokine controlling the proliferative response of CD4 lymphocytes. The proliferation of purified CD4 lymphocytes stimulated by anti-CD3 is completely neutralized by anti-IL-2 monoclonal antibodies.

B lymphocytes

Activated B lymphocytes express the high-affinity IL-2 receptor and respond to IL-2. Under these conditions they proliferate intensively and produce immunoglobulins of the IgM, IgG and IgA isotypes. Different stimulations can induce the susceptibility of B lymphocytes to IL-2. Experimentally anti-Ig, or lipopolysaccharides (LPS) are good stimulators. Physiologically, in the context of T/B collaboration Th1 lymphocytes (or THl-like in humans) may induce an intense proliferation and differentiation of the B lymphocyte population. Unlike IL-4, IL-5 and transforming growth factor (3 (TGF(3), IL-2 does not exert an influence on isotype selection.

Natural killer (NK) cells

All NK cells are spontaneously sensitive to IL-2. In the majority of these cells IL-2 can stimulate cytotoxic activity without stimulating NK cell proliferation. In rare NK cells, expressing the high-affinity IL-2R, IL-2 stimulates both cytotoxic and proliferative responses. NK cells play a dominant role as the first defense barrier against viral infections and tumor growth.

Monocytes

IL-2 spontaneously stimulates the killing of tumor cells and bacteria by monocytes. Interferon y (IFNy) and LPS stimulate the appearance of high-affinity IL-2R on the surface of monocytes and therefore increase sensitivity to IL-2. During IL-2 stimulation monocytes produce a large array of mediators such as H202, prostaglandin E2 (PGE2), thromboxane B>, and tumor necrosis factor a (TNFa). These products may be responsible for the side-effects observed during IL-2 therapy.

Granulocytes

Neutrophils are also sensitive to IL-2. Their antifungal activity is greatly enhanced by IL-2, perhaps because of the production of lactoferrin and TNFa by these cells.

IL-2 is a pleiotropic cytokine with proinflammatory activity both on the nonspecific arm of the immune system (NK cells, monocytes) and on the specific response generated by T and B cells.

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