Interleukin-2 and human monocyte activation

Abstract

The recognition of the monocyte/macrophage-activating properties of IL-2 has broadened our image of the biological effects of this lymphokine from those of a T cell growth factor to those of a molecule with pleiotropic effects. The detailed analysis of the mechanisms of action of IL-2 including its biological effects on different cell types and the regulation of its receptors has increased dramatically the spectrum of the biological responses that can be modified by IL-2. The regulation of the expression of the IL-2 receptor subunits differs in terms of response to extracellular stimuli and intracellular control, suggesting that the response to IL-2 will vary depending on the nature and extent of environmental stimulation. Furthermore, the fact that the IL-2R gamma chain can be part of the receptor for IL-4, IL-7, and perhaps other cytokines indicates that IL-2 may modulate the response of monocytes simply by binding or releasing the IL-2R gamma chain and thus modulating the responsiveness to IL-4 or IL-7. Conversely, the extent of utilization of IL-2R gamma chain by various cytokines may dictate the monocytic response to IL-2. In fact, the availability of IL-2R gamma chain seems to be the limiting factor in the response of monocytes to IL-2. Modulation of cytokine receptors is an integral part of the control of the IL-2 response. The induction of CSF-1 receptor by IL-2 and the positive effect of CSF-1 on the duration of the cytotoxic response in IL-2-stimulated monocytes are an interesting example of a synergistic interaction of potential physiological relevance. The response of monocytes to IL-2 can also be modulated by inhibitory circuits, such as those involving TGF-beta 1, IFN-gamma, and IL-4. However, IFN-gamma and IL-4 can also activate monocytes and the timing and relative concentrations of the various cytokines may be critical variables in determining the ultimate monocyte phenotype. These studies have given us a glimpse of a very complex picture composed of multiple backgrounds and several players. However, the present information is not sufficient to make meaningful predictions of the resulting monocyte phenotype in an inflammatory reaction in which multiple cytokines are involved.(ABSTRACT TRUNCATED AT 400 WORDS)

Monocyte Surface-Bound IL-15 Can Function as an Activating Receptor and Participate in Reverse Signaling

“…The activity of these cytokines on monocytes is not mitogenic, but instead modulates cellular function (53). For example, treatment of monocytes with IL-2 will activate tumor cytocidal programs (54).…”

Interleukin-2 induces development of dendritic cells from cord blood CD34+ cells

“…The IL-2␤ chain is critical for IL-2 activation of monocytes and is expressed in more than 90% of these cells. It has been suggested that IL-2R␣ is important for the formation of high-affinity binding sites responding to IL-2 [41][42][43]. Although the IL-2R␤ chain is shared with IL-15 receptor, and IL-2R␥ chain is also common to IL-4, IL-7, IL-9, and IL-15 [23], we studied the expression of all three IL-2R subunits.…”

Antibody–cytokine fusion proteins: applications in cancer therapy

“…This cytokine has diverse stimulatory effects on a variety of immune cells including the activation of natural killer (NK) cells, induction of the lymphokine-activated killer (LAK) cells [43], activation of monocytes [44] and macrophages [42], and the activation of CD8 + cytotoxic T lymphocytes (CTLs) [45]. Previous studies have shown that IL-2 can induce T-cell production of IFN-γ [46], a very potent immunomodulator that can inhibit tumor growth by direct induction of apoptosis [47], and through its ability to stimulate CTLs [48], macrophages [49], NK cells [50] and to increase the expression of the major histocompatibility complex class II molecules (MHC class II) [51].…”