ABSTRACT
Autoimmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 8.3 Human IL2/IL2R Polymorphisms in Multifactorial Conditions . . . . . . . . . . . . . . . . . . 111
8.3.1 Human IL2 Polymorphisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 8.3.1.1 The 330 Promoter (rs2069762) SNP: Effect on IL-2 Expression 112 8.3.1.2 The 330 (rs2069762) SNP and Disease Association Studies . . . . 114
8.3.2 Human IL2 Receptor Alpha Gene Polymorphisms (hIL2RA) . . . . . . . . . . . . 115 8.3.3 Human IL2 Receptor Beta Gene Polymorphisms (hIL2RB) . . . . . . . . . . . . . . 115 8.3.4 IL2 Receptor Gamma Chain Gene Polymorphisms (hIL2RG). . . . . . . . . . . . 115
8.4 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
Interleukin 2 (IL-2) is involved in the expansion of the immune system as a potent T cell growth factor and on the other hand is also a major contraction factor implicated in apoptosis or activation-induced cell death (AICD) by FAS-and tumor necrosis factor (TNF)-dependent pathways.1 The activity of IL-2 is essential for the generation, expansion, survival, and functioning of CD4þ CD25þ regulatory T cells (Treg).2-4 It is known that impaired production of Treg cells is sufficient to account for the unexpected lethal autoimmunity that is associated with IL-2-, IL-2Ra-and IL-2Rb-deficient mice.3,5 Treg cells have emerged as one of the major populations that suppress TCR-induced proliferation of CD4 and CD8 T cells in vitro and in vivo and have been shown to prevent autoimmune diseases, allograft rejection, and to down-regulate immune responses against antigens and pathogens.6-8 In vitro studies have shown that Treg cells fail to proliferate when stimulated via their TCR even in the presence of a co-stimulatory signal by anti-CD28 due to a failure to transcribe their IL2 gene. Therefore, they need exogenous IL-2 (paracrine), although about ten-fold higher concentrations of IL-2 are required to generate a level of proliferation equivalent to that seen with CD4þCD25 T cells and higher level for induction of suppressor activity. When the suppressive activities of cells grown in the presence of different cytokines are compared, only cells grown in the presence of IL-2 and IL-4 were potent suppressor cells. Nevertheless, promotion of T cell proliferation and activation of several effector cells is the rational base for the pharmacological utilization of IL-2 in cancer patients, especially those with metastatic melanoma, acute myelogenous leukaemia,
or metastatic renal-cell carcinoma, as well as in renal and heart transplant recipients. IL-2 is used, in addition, to boost immunity in individuals infected with HIV and in patients with AIDS.
