Disease relevance of IL7

• These results suggest that IL7 may, therefore, represent an important cytokine in the physiopathology of cutaneous T cell lymphoma [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-7-treated naive T cells can be productively infected by T-cell-adapted and primary isolates of human immunodeficiency virus 1 [3].
• Using cell culture techniques, reverse transcriptase-polymerase chain reaction (RT-PCR), and immunhistochemistry we found that IL-15, like IL-7, is a growth factor for the Sézary cell line SeAx and that both cytokines prolonged the survival of malignant T cells directly isolated from Sézary syndrome (SS) patients [4].
• RESULTS: Freshly isolated cells from RA synovial tissues more strongly expressed mRNA for both IL-7 and IL-15 compared with the cells from osteoarthritis tissues, and could spontaneously release greater amounts of these cytokine proteins in culture [5].

Psychiatry related information on IL7

• The authors now investigated the possible role of IL-7 in HIV-1-associated dementia (HAD) [6].
• METHODS: Plasma IL-7 levels were measured, by enzyme-linked immunoassay, in patients with primary, chronic, or long-term nonprogressive HIV-1 infection (PHI, CHI, and LTNP, respectively) before and after 40-48 weeks of antiretroviral therapy (ART) [7].
• Modalities of interleukin-7-induced human immunodeficiency virus permissiveness in quiescent T lymphocytes [8].
• Moreover IL-7, a newly cloned lymphokine, was found to support the growth and expansion of the human nature T cells [9].

High impact information on IL7

• Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis [10].
• IL-2, IL-15, and IL-7 are cytokines that are critical for regulating lymphoid homeostasis [10].
• The control of CD4+ memory T cells is more mysterious, with roles reported for IL-7 and/or contact via the TCR [11].
• In addition, several cDNA clones were isolated that encode a secreted form of the human IL-7 receptor capable of binding IL-7 in solution [12].
• cDNA clones encoding the human and murine interleukin-7 (IL-7) receptor were isolated and expressed in COS-7 cells [12].

Chemical compound and disease context of IL7

• Interleukin-7, reported to be a crucial cofactor of tumor necrosis factor (TNF) to promote HIV replication, is shown here to counteract the apoptotic activity of TNF [13].
• Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells [14].
• Remarkably, the IL-12-conditioned CD8 T cells demonstrate increased sensitivity to IL-7 and IL-15, whereby they are rendered "fit" for homeostatic self-renewal as well as augmented CD4-dependent recall responses that are effective at controlling Salmonella infection in vivo [15].
• Changes in eosinophil and leukocyte infiltration and expression of IL-6 and IL-7 messenger RNA in mite allergen patch test reactions in atopic dermatitis [16].
• Blocking NFAT activity using a number of reagents, such as Cyclosporin A, FK-506, or the NFAT-specific inhibitor known as VIVIT peptide, all markedly reduced IL-7-mediated induction of HIV replication in naive T cells [17].

Biological context of IL7

• Growth of Sézary cell lines was shown to be strictly dependent on IL7, and after 2-5 wk of culture presented a switch to a homogeneous phenotype CD3+4+8-7- (except for one line that remained CD7+), with a typical morphology of Sézary cells [1].
• Two patients with evidence of synergistic stimulation of [3H]-TdR incorporation showed IL7-R gene expression by RT-PCR and IL7 affinity cross-linking [2].
• IL-7 and IL-15 also supported the growth of SeAx cells in the presence of the apoptosis inducing agents dexamethasone and retinoic acid [4].
• Our data confirm the pivotal role of IL-2 and IL-7 in the regulation of T-lymphocyte homeostasis in HIV infection [18].
• Interleukin-7 (IL-7) and IL-15 have been recently identified as growth factors for cutaneous T-cell lymphoma (CTCL) cells, and they protect these cells from cell death [19].

Anatomical context of IL7

• By neutralisation of IL12 in MC cultures, indirect effects of IL7 on T cells through accessory cells were studied [20].
• Direct effects of IL7 on isolated synovial fluid (SF) CD4+ T cells were studied by cytokine analysis [20].
• Our data suggest that IL-7, in addition to regulating lymphocyte growth and differentiation, has potent effects on cells of the monocytic lineage [21].
• Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes [21].
• IL-7 was found to induce the generation of both CTL and LAK cells in bulk cultures [22].

Associations of IL7 with chemical compounds

• An optimal concentration of IL-7 (100 ng/ml) induced monocytes to secrete 10-fold more IL-6 than an optimal concentration of IL-1 beta (10 ng/ml), and almost as much as LPS [21].
• Interleukin-7 (IL-7) is a glycoprotein that regulates lymphocyte precursor growth and differentiation [23].
• Tyrosine phosphorylation of several proteins (55 kd, 30 kd, and 24 kd) in HS-27a cells was rapidly increased after incubation with recombinant IL-7 [24].
• We also show that the IL-7-induced enhancement of the AP-1-DNA binding activity is not cyclosporin A-sensitive [25].
• Quality analysis of the hIL-7 model identified poor structural features in the carboxyl terminus that, when further studied using hydrophobic moment analysis, detected an atypical structural property in helix D, which contains Cys 130 and Cys142 [26].

Physical interactions of IL7

• On the basis of the RT-PCR reaction, molecular weight estimated in Western blot and IL-7 binding activity the identified endothelial IL-7 receptor was identical to the lymphocyte-type IL7-R [27].
• The molecular mechanisms underlying the IL-7 effect involve the upregulation of the DNA binding activity of NFAT (60%) and AP-1 (120%), without affecting the activities of NFkappaB and CD28RC, which was confirmed by transfection assays [25].
• Costimulation with Con A plus IL-7 stabilized both transcripts to t1/2 of greater than 2 h for IL-3 mRNA and 90 min for GM-CSF mRNA [28].
• We demonstrate that surface psi L expression is considerably enhanced upon interleukin-7 stimulation and that the psi L complex is formed independently of the Ig alpha/Ig beta heterodimer [29].
• Induction of T cell adhesion to extracellular matrix or endothelial cell ligands by soluble or matrix-bound interleukin-7 [30].

Regulatory relationships of IL7

• Interleukin 7 enhances cytolytic T lymphocyte generation and induces lymphokine-activated killer cells from human peripheral blood [22].
• In contrast to the low concentrations of IL-7 required to stimulate T cell growth and differentiation (as low as 0.1 ng/ml), relatively high concentrations of IL-7 were necessary to induce IL-6 secretion by monocytes (at least 10 ng/ml) [21].
• Interleukin-7 (IL-7) enhances class switching to IgE and IgG4 in the presence of T cells via IL-9 and sCD23 [31].
• Incubation of all seven patients' cells with IL7 induced coexpression to varying degrees of IL7-R and IL2-R [2].
• However, PHA-induced CD23 expression was enhanced by costimulation with IL-7 (1,000 U/ml) [32].
• Down-regulation of IL-7Ralpha on TCR/CD28-activated cells limited IL-7 responsiveness [33].

Other interactions of IL7

• In contrast to its effects on CTL generation, the induction of LAK cells by IL-7 was virtually independent of IL-2 [22].
• Limiting dilution analysis indicated that IL-2 stimulated fivefold more LAK-P than IL-7 and 220-fold more than IL-4 [22].
• Detailed examination revealed that, among PBMC, monocytes, rather than lymphocytes, were secreting IL-6 in response to IL-7 [21].
• Constitutive and interleukin-7/interleukin-15 stimulated DNA binding of Myc, Jun, and novel Myc-like proteins in cutaneous T-cell lymphoma cells [34].
• JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of phosphatidylinositol-3' kinase [35].

Analytical, diagnostic and therapeutic context of IL7

• Sézary lymphoma cells from at least three of five patients studied expressed IL7 mRNA, and skin from three of five patients studied, as well as normal skin, expressed IL7 mRNA by RT-PCR [2].
• Collectively, these data suggest that IL-7 has potent regulatory effects on human cytolytic cell populations and, either alone or in combination with other cytokines, could be important for the in vitro expansion of cells for adoptive immunotherapy [22].
• IL-7 production was measured by immunoassay [2].
• PBMC were obtained from 15 patients 27 to 84 days after autologous (n = 13) or syngeneic (n = 2) bone marrow transplantation (BMT) and tested for IL-7-induced LAK activity [36].
• Flow cytometry revealed an increase in IL-2-receptor-positive lymphocytes following incubation with IL-7 [37].

References