Interleukin-2 (IL-2) is expressed in E. coli and has been engineered to contain the serine for cysteine substitution found
in Proleukin® (aldesleukin).
Recombinant IL-2 is
widely used in cell culture for the expansion of T cells. IL-2 is expressed by CD4+ and CD8+ T cells, gamma delta T cells, B cells, dendritic cells, and eosinophils (1-3). Mature human IL-2 shares 56% and 66% amino acid (aa) sequence identity with mouse and rat IL-2, respectively. Human and mouse IL-2 exhibit cross-species activity (4). The receptor for IL-2 consists of three subunits that are present on the cell surface in varying preformed complexes (5-7). The 55 kDa IL-2 R alpha is specific for IL-2 and binds with low affinity. The 75 kDa IL-2 R beta, which is also a component of the IL-15 receptor, binds IL-2 with intermediate affinity. The 64 kDa common gamma chain gammac/IL-2 R gamma, which is shared with the receptors for IL-4, -7, -9, -15, and -21, does not independently interact with IL-2. Upon ligand binding, signal transduction is performed by both IL-2 R beta and gammac.
IL-2 is best known for its autocrine and paracrine activity on T cells. It drives resting T cells to proliferate and induces IL-2 and IL-2 R alpha synthesis (1, 2). It contributes to T cell homeostasis by promoting the Fas-induced death of naïve CD4+ T cells but not activated CD4+ memory lymphocytes (8). IL-2 plays a central role in the expansion and maintenance of regulatory T cells, although it inhibits the development of Th17 polarized cells (9-11). Thus, IL-2 may be a key cytokine in the natural suppression of autoimmunity (12, 13).
IL-2 expression and concentration can have either
immunostimulatory effects at high doses or immunosuppressive effects at low
doses due to its preferential binding to different receptor subunits expressed
by various immune cell types. This has led to the generation of recombinant
IL-2 variants aimed at modifying IL-2 receptor binding for increased antitumor
efficacy (14, 15). These variants are typically used in combination with immune
checkpoint inhibitors instead of as a monotherapy (14). IL-2 can be genetically
engineered to express in NK cells for CAR T cell therapies, and in combination
with other cytokines like IL-15, can increase cell viability and proliferation
(16). In addition to adoptive cell transfer and checkpoint blockade inhibitors,
cancer vaccines that boost immune responses have been combined with IL-2
treatment with promising results in recent
In cell culture, IL-2 is a frequently used cytokine for the
proliferation, differentiation, and increased antibody secretion of B cells as
they transform into plasma cells in vitro (17). IL-2 is also a classically used
cytokine for the expansion of NK cells, early differentiated T cells and
effector memory Treg cells for adoptive cell transfer cancer immunotherapy (16,
18). GMP IL-2 is a commonly used supplement for the expansion of these cell
types for cellular therapies.