Disease relevance of CD70

• Impaired up-regulation of CD70 and CD86 in naive (CD27-) B cells from patients with common variable immunodeficiency (CVID) [1].
• We identified CD70 as a radioinducible gene in U87 MG glioma cells [2].
• Identification of CD70-mediated apoptosis of immune effector cells as a novel immune escape pathway of human glioblastoma [2].
• Two human neuroblastoma cell lines did not express CD70 [2].
• CD70 protein was also detected by immunocytochemistry in 5 of 12 glioblastomas and 3 of 4 anaplastic astrocytomas in vivo [2].

High impact information on CD70

• Both CD70 and TNF induce recruitment of the IKK kinase complex to their receptors [3].
• The interaction between the TNF receptor family member CD27 and its ligand CD70 provides a costimulatory signal for T cell expansion [4].
• B cell numbers in CD70 transgenic (TG) mice progressively decreased in primary and secondary lymphoid organs [4].
• Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions [5].
• CD27 and CD70 in T cell and B cell activation [6].

Chemical compound and disease context of CD70

• No alteration in CD70 expression was observed after glioma cell exposure to cytotoxic drugs such as lomustine [2].
• CD70 (TNFSF7) is a B cell costimulatory molecule overexpressed on CD4(+) lupus T cells as well as procainamide and hydralazine treated T cells, and contributes to excessive B cell stimulation in vitro and in lupus [7].

Biological context of CD70

• The 2F2 mAb enabled us to begin to analyze the biochemical properties, tissue distribution, and function of the CD27L on human cells [8].
• Down-regulation of CD27 from the T cell surface by recombinant CD27L was shown to be at least partially caused by release of soluble CD27 [8].
• CD27 but not CD70 and 4-1BB intragraft gene expression is a risk factor for acute cardiac allograft rejection in humans [9].
• Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors [10].
• Recent data, however, show that during chronic lymphocyte choriomeningitis virus (LCMV) infection, triggering of the costimulatory receptor CD27 by its ligand CD70 impedes neutralizing antibody production and leads to viral persistence [11].

Anatomical context of CD70

• Based on these observations, we hypothesized that a ligand for CD27L is expressed on B cell lines and that ligand interaction would result in down-modulation of the molecule from the T cell surface [8].
• CD70 is a surface Ag found on activated but not resting T and B lymphocytes [12].
• Phenotypical analyses showed that freshly isolated lymphocytes lacked CD27L expression, but that expression of the molecule could be induced after in vitro stimulation of T and B cells [8].
• Enhancement of allospecific CTL generation was also observed when CD27L/CD70-expressing membranes were added only during the last 24 to 48 h of 5-day MLC [13].
• To study the role of CD27-CD27 ligand (CD27L)/CD70 interactions in the generation of murine allospecific T cell responses, SF9 cells or cell membranes expressing recombinant human CD70 were added to in vitro MLC containing C57BL/6 (H-2b) responder cells and class I and II MHC disparate H-2b/d stimulator cells [13].

Associations of CD70 with chemical compounds

• Human CD70 (CD27 ligand) is a type II transmembrane glycoprotein belonging to the TNF family [14].
• Lipopolysaccharide stimulation converts vigorously washed dendritic cells (DCs) to nonexhausted DCs expressing CD70 and evoking long-lasting type 1 T cell responses [15].
• CD70, CD27 ligand, is a TNF related trans-membrane protein induced upon activation on T and B cells [16].
• PMA + Ionomycin induced CD70 on the large majority of CD8+ cells, but only on a minority of CD4+ cells (P < 0.002), and among these, preferentially on the CD45R0+ subset compared with the CD45RA+ [17].
• Anti-CD70 antibody-drug conjugates (ADC) consisting of auristatin phenylalanine phenylenediamine (AFP) or monomethyl auristatin phenylalanine (MMAF), two novel derivatives of the anti-tubulin agent auristatin, mediated potent antigen-dependent cytotoxicity in CD70-expressing RCC cells [18].

Regulatory relationships of CD70

• Thus, induction of B-cell and T-cell apoptosis via interactions of CD70 expressed on glioma cells and CD27 expressed on B and T cells may be a novel way for the immune escape of malignant gliomas [2].
• CD70 mRNA expression was enhanced by irradiation in 8 of 12 glioma cell lines in a p53-independent manner [2].
• CD27-CD70 interactions regulate B-cell activation by T cells [19].
• CD70 was found to be expressed almost equally on both activated CD4 and CD8 T cells [20].
• Therefore, it is concluded that CD70 expressed on ELD-1 cells has a crucial role in stimulating IFN-gamma production by CD8+ T cells through an alternative pathway which does not require CD4+ T-cell help or CD28-B7 interactions [21].

Other interactions of CD70

• Among induced genes, four (TNFR1, TNFSF7, caspase-8, and DAPK1) were associated with the tumor necrosis factor ligand-receptor death pathway [22].
• The cloning of CD70 and its identification as the ligand for CD27 [12].
• Induction of TNFR1, TNFSF7, and caspase-8 were confirmed by Northern and Western analyses [22].
• Interestingly, only the molecules CD25, CD70 and CD86, all relevant in cognate T-B interaction, showed a significantly lower expression in naive B cells from CVID patients compared to controls [1].
• Characterization of the human CD27 ligand, a novel member of the TNF gene family [8].

Analytical, diagnostic and therapeutic context of CD70

• Bioassays demonstrated that the CD70 cDNA clone expressed in African green monkey kidney cells would induce the proliferation of PHA-costimulated T cells [12].
• Neutralization of CD70 expressed on glioma cells prevented apoptosis and enhanced the release of tumor necrosis factor-alpha in cocultures of glioma cells and PBMCs [2].
• To provide the functional capacity of CD27 molecule on NK cells, we here highly purified CD3- CD56+ NK cells by flow cytometry (purity > 98%), and investigated their NK cell activity via CD27/CD70 interaction using a CD70-transfectant by a 4 h 51Cr-release assay [23].
• Proliferation response of leukemic cells to CD70 ligation oscillates with recurrent remission and relapse in a low-grade lymphoma [24].
• Modulation by IL-2 of CD70 and CD27 expression on CD8+ T cells: importance for the therapeutic effectiveness of cell transfer immunotherapy [25].

References