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Gene Review

IL2  -  interleukin 2

Homo sapiens

Synonyms: IL-2, Interleukin-2, T-cell growth factor, TCGF, lymphokine
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Disease relevance of IL2

  • In 12 of 17 patients with aplastic anemia, interleukin 2 (IL2) production was markedly elevated in vitro (P less than .01 by paired statistical analysis) [1].
  • RESULTS: Sézary lymphoma cells from seven patients showed synergistic (five of seven) or additive (two of seven) proliferation when cultured in the presence of IL2 and IL7, as compared with culture with either cytokine alone [2].
  • Interleukin 2 (IL2) was injected peritumorally and intranodally in 36 patients with unresectable squamous cell carcinoma of the head and neck enrolled in an Eastern Cooperative Oncology Group-sponsored phase Ib trial (EST P-Z388) [3].
  • These results suggest that IL2 and IFN-gamma could enhance colonic epithelial cell injury mediated by the ADCC mechanism in ulcerative colitis and that ADCC enhanced by cytokines is restored by PSL treatment [4].
  • In 15 of 21 (71%) melanomas and 2 of 9 (22%) benign cutaneous lesions, we found uptake of 99mTc-IL2 [5].
  • A good correlation was found between IL-2 and TNF-alpha levels and the number of metastases and pain score [6].

Psychiatry related information on IL2


High impact information on IL2

  • Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis [12].
  • IL-2 is necessary to destroy self-reactive lymphocytes and thus favors peripheral tolerance to self-antigens, whereas IL-15 favors the persistence of lymphocytes involved in the memory and effector responses to invading pathogens but risks the development of inflammatory autoimmune diseases [13].
  • The former arises from incomplete T cell activation, is mostly observed in previously activated T cells, is maintained by a block in the Ras/MAP kinase pathway, can be reversed by IL-2 or anti-OX40 signaling, and usually does not result in the inhibition of effector functions [14].
  • Productive engagement of T cells by antigen-presenting cells (APCs) results in recruitment of PKC theta to the T cell-APC contact area--the immunological synapse--where it interacts with several signaling molecules to induce activation signals essential for productive T cell activation and IL-2 production [15].
  • T cell apoptosis occurs in at least two major forms: antigen-driven and lymphokine withdrawal [16].

Chemical compound and disease context of IL2

  • These results suggest that BCG-MUC1-IL2 preferentially induces MUC1-specific cellular immune responses and it may serve as a vaccine for breast cancer prevention and treatment [17].
  • In human corticotrophic adenoma cells, basal IL-2 mRNA expression as well as IL-2 secretion were further stimulated by phorbol myristate acetate [18].
  • 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine [19].
  • Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro [20].
  • IL-7 or IL-2 induced the proliferation of some leukemic cells, whereas sequential cell treatment with CD2-MoAb and then IL-2 promoted CD3/TCR expression on nearly all CD2+ cells (15 of 16), except for 1 T-ALL that developed into CD3-CD16+CD56+ cells [21].

Biological context of IL2

  • The stable integration of the IL2 gene did not modify the phenotype of the leukemic cells, the expression of the IL2 receptor alpha and beta chains and of several cytokine genes, or the kinetics of in vitro growth and proliferation [22].
  • These results suggest that IL-4 may regulate development and function of T-cell subsets involved in cell-mediated immunity in part by inhibiting factors required for transcription of the IL2 gene [23].
  • Cell proliferation was accompanied by production of IL2 to levels that were, in some cases, similar to those obtained with lectin stimulation [1].
  • These studies examined the effect of the calcium ionophore ionomycin, an enhancer of cytoplasmic [Ca2+] levels, on IL2 and IL4-mediated proliferation of anti-mu-stimulated normal human B cells [24].
  • Thus, IFN-alpha can positively interact with a well defined interleukin, IL2, at a pre or post receptor level to potentiate antibody response [25].

Anatomical context of IL2

  • RESULTS: The productive insertion of the IL2 gene was achieved in all three cell lines studied [22].
  • These findings have prompted investigations into whether human tumor cells may be transduced with the IL2 gene and whether tumor cell lines could be engineered to release IL2 [22].
  • IL-4 pretreatment of Jurkat cells prior to stimulation resulted in a decrease in transcription of the IL2 gene [23].
  • In normal human peripheral blood lymphocytes (PBL), IL4 does not induce LAK activity and inhibits LAK induction by IL2 [26].
  • In the tumor parenchyma, NK cells (P = 0.0001) and HLA-DR+ cells (P = 0.003) were increased after IL2 therapy [3].

Associations of IL2 with chemical compounds

  • However, while IL2 expression requires the contribution of Ca(2+)- and protein kinase C-dependent signals, we report that activation of human IL4 transcription through the Ca(2+)-dependent pathway is diminished by protein kinase C stimulation in Jurkat T cells [27].
  • These findings suggest that IL2R beta is a substrate for the tyrosine kinase which is activated by IL2 binding to its receptor [28].
  • Two different antibodies reactive with phosphotyrosine specifically immunoprecipitated IL2R beta cross-linked to radiolabeled IL2 [28].
  • These results suggest that putative protein kinase C activation, either by direct treatment with phorbol ester or during IL2 signaling, counteracts the inhibitory effects of ionomycin [24].
  • Moreover, analysis of phosphatidylinositol and phosphatidic acid metabolic changes mediated by each signal separately or together suggests that, in this model, IL2 increases the phosphoinositide turnover induced by anti-CD2 antibodies up to a level required for helper function acquisition [29].
  • Overexpression of either antisense CREM or CREB plasmid rescued morphine-induced inhibition of IL-2 promoter activity and protein production [30].
  • The recommended dose of L19-IL2 in combination with dacarbazine was defined as 22.5 Mio IU [31].

Physical interactions of IL2

  • GM2 and GM3 each inhibited Ig production, thymidine uptake, and TNF-alpha production by surface IgG1+ (slG1+), sIgG2+, sIgG3+, sIgG4+, and sIgM+ B cells without affecting IL-2 binding or TNF-alpha binding to B cells, but had no such inhibitory effects on sIgA1+ or sIgA2+ B cells [32].
  • Costimulation by B7-1 and LFA-3 targets distinct nuclear factors that bind to the interleukin-2 promoter: B7-1 negatively regulates LFA-3-induced NF-AT DNA binding [33].
  • Accordingly, induction of IL-2 secretion upon receptor cross-linking by membrane-bound antigen requires CD28/B7 costimulation whereas IFN-gamma secretion and cell proliferation does not [34].
  • Interaction of interleukin 2 (IL2) with its high affinity membrane receptor complex (IL2R) is sufficient to induce proliferation of T lymphocytes [28].
  • Although the IL-2 CD28RE exerted selective binding with c-Rel and c-Rel/NFKB1, the other CD28REs allowed efficient binding of a wide range of NF-kappaB/Rel family proteins [35].

Enzymatic interactions of IL2


Co-localisations of IL2

  • ICAM-1 expression on follicular epithelium co-localized with intraepithelial mononuclear cells (MNC) positive for the interleukin-2 receptor alpha-chain (IL-2R) or HLA-DR [41].

Regulatory relationships of IL2


Other interactions of IL2

  • Interleukin 15 (IL-15) is a novel cytokine with interleukin-2-like activity [46].
  • Certain combinations of monoclonal antibodies to CD2 epitopes trigger proliferation of peripheral blood T lymphocytes, cytotoxic effector function and expression of IL-2 receptors by thymocytes, resulting in thymocyte proliferation in the presence of exogenous IL-2 (ref. 11) [47].
  • Although only 26 percent identical to B7-1, B7-2 also costimulates IL-2 production and T cell proliferation [48].
  • CD28 costimulatory signals are required for lymphokine production and T cell proliferation [49].
  • The proximal conserved element (-73 to -48 bp) shares homology with the NFIL-2A element in the IL-2 promoter; these elements compete for binding of factors in Jurkat nuclear extracts, although the NFIL-2A element but not the IFN-gamma element binds Oct-1 [50].

Analytical, diagnostic and therapeutic context of IL2

  • Messenger RNA expression of the IL2 gene was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and productive IL2 release using a human IL2 assay and an enzyme-linked immunosorbent assay kit [22].
  • By flow cytometry, TIL recovered from post-IL2 biopsy tissues were enriched (P < 0.05) in CD3-CD56+ (NK) cells [3].
  • Immunophenotyping of TIL performed on cryostat sections of paired pre- and post-IL2 biopsy tissues showed increases after IL2 therapy in the number of T-cells (P = 0.005), natural killer (NK; CD16+) cells (P = 0.0001), CD25+ cells (P = 0.004), and HLA-DR+ cells (P = 0.001) accumulating in the tumor stroma [3].
  • The degree of such infiltration and cell activation are considered significant prognostic factors reflecting the host's immune response to the tumor; thus, patients with peritumoral infiltration may have a better prognosis and may also achieve a better response to interleukin-2 (IL2) immunotherapy [5].
  • This latter, prepared by a combination of absorption on concanavalin A-Sepharose and gel filtration, was IL2 free and unable to support the anti-TNP response [51].


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