Interleukin-2: from T cell growth and homeostasis to immune reconstitution of HIV patients.

Interleukin (IL)-2 was initially described as a major stimulant of T lymphocytes in vitro. Later, the characterization of IL-2 knockout animals showed that the ability to stimulate T cells could be replaced by other cytokines. In vivo, IL-2 plays a unique role in controlling lymphoproliferation. This is partly explained by its role in the generation and maintenance of T regulatory cells (Treg). In HIV-infected patients, the IL-2/IL-2 receptor (IL-2R) system is dysregulated. The fact that IL-2 is underproduced along with defective IL-2R signaling detected in patient lymphocytes, may explain the progressive impairment of the immune system that occurs during chronic infection with this virus. These defects are partly reversed by highly active antiretroviral therapy (HAART). However, in some patients IL-2R defects persist and the CD4 counts remain low despite good control of the viral load. These patients benefit from HAART given in conjunction with IL-2 therapy.