Schwerd et al. report a novel homozygous missense substitution in the cytokine co-receptor GP130 encoded by IL6ST. This is associated with defective IL-6, IL-11, OSM, and IL-27 signaling and causes immunodeficiency and skeletal abnormalities with similarities to STAT3 hyper-IgE syndrome.

Transduction of dendritic cells (DC) can result in presenmixed lymphocyte reactions. Mice immunized with Adtation of tumor-associated antigens and induction of transduced DC develop cytotoxic T lymphocytes that are immunity against undefined epitopes. The present studies specific for the ␤-galactosidase or DF3/MUC1 antigens. demonstrate adenovirus (Ad)-mediated transduction of the The results also demonstrate that Ad.MUC1-transduced ␤-galactosidase gene in mouse DC. Similar transductions DC induce a specific response which inhibits the growth have been obtained with the gene encoding the of DF3/MUC1-positive tumors. These findings support the DF3/MUC1 tumor-associated antigen. We show that the usefulness of Ad-transduced DC for in vivo immunization Ad-transduced DC are functional in primary allogeneic against tumor-associated antigens. Results and discussionT cells. 1 Murine DC pulsed with peptides prime antigenspecific CD8 + cytotoxic T lymphocytes (CTLs) in vivo. 2 Flow cytometry was used to define the phenotype of DC Peptides derived from tumor-associated antigens have following transduction with recombinant adenovirus. DC similarly been used to pulse DC and induce antitumor derived from bone marrow expressed MHC class I and II immunity. [3][4][5] Other studies have employed soluble products, costimulatory molecules and ICAM-1 18 (Figure tumor-associated antigens for loading DC and generating 1a). Transduction with Ad.␤gal resulted in a similar patantitumor activity. 6 Whereas peptides pulsed on to DC tern of antigen expression ( Figure 1a). Moreover, transmay dissociate from MHC molecules, CD34 + cells have duction with Ad.MUC1 was associated with DF3/MUC1 been retrovirally transduced to stably express antigens expression and little if any effect on cell surface levels of after differentiation to DC. 7,8 In contrast to pulsing, trans-MHC, costimulatory or adhesion molecules ( Figure 1a). duction of DC can result in longer term antigen presenThe Ad.MUC1-transduced DC exhibited a typical mortation and induction of immunity against undefined phology with veiled dendrites (Figure 1b). Staining with MHC epitopes. Thus, transduced DC may be effective in MAb M5/114 (anti-MHC class II) and MAb DF3 demonimmunizing against known tumor-associated antigens. strated expression of DF3/MUC1 by the transduced DC The human DF3/MUC1 glycoprotein is aberrantly (Figure 1b). Immunoblot analysis of the Ad.MUC1 transoverexpressed in breast and other carcinomas. 9 The DF3 duced DC confirmed DF3/MUC1 expression ( Figure 1c). protein is one member of the MUC1 family of carcinomaWhereas MAb DF3 detects glycosylated MUC1, the findassociated antigens that contain variable numbers of ing that MAb DF3-P reacts with an approximately 55 kDa highly conserved (G+C)-rich 60 base pair tandem protein in the transduced DC also provides support for repeats. 10,11 A C-terminal region includes a transmemdetection of the unglycosylated protein core 19 ( Figure 1c). brane domain that anchors the antigen at the cell sur-DC are potent stimulators ...