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Interleukin-2 fusion protein (DAB389IL-2) selectively targets activated human peripheral blood and lamina propria lymphocytes. 1997

A Bousvaros, and A C Stevens, and T B Strom, and J Murphy, and J T Lamont
Combined Program in Pediatric Gastroenterology and Nutrition, Children's Hospital, Boston, Massachusetts, USA.

Activated mucosal T lymphocytes correlate with the intestinal inflammation of inflammatory bowel disease. Activated T cells elaborate interferon-gamma (IFN-gamma) and express high-affinity interleukin-2 (IL-2) receptors. The IL-2/diphtheria toxin fusion protein (DAB389IL-2) has been shown to specifically kill high affinity IL-2 receptor-bearing cells. We tested whether DAB389IL-2 could specifically target activated lamina propria lymphocytes. Lymphocytes were activated in vitro with phytohemagglutinin and IL-2 for 24-48 hr. Toxin efficacy was determined by the [14C]leucine incorporation, IFN-gamma ELISA, and flow cytometry. DAB389IL-2 (10(-11) M) inhibited protein synthesis by 80% in activated lamina propria lymphocytes. This inhibition was blocked by coculture of either excess IL-2 or a nonfunctional IL-2 diphtheria toxin mutant protein. DAB389IL-2 (10(-12) M) also significantly reduced the numbers of activated helper T cells and IFN-gamma levels in 24-hr cultures. DAB389IL-2 specifically targets activated IL-2 receptor-positive lamina propria lymphocytes and is a potential new therapeutic agent for patients with active inflammatory bowel disease.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D007413 Intestinal Mucosa Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI. Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D004167 Diphtheria Toxin An ADP-ribosylating polypeptide produced by CORYNEBACTERIUM DIPHTHERIAE that causes the signs and symptoms of DIPHTHERIA. It can be broken into two unequal domains: the smaller, catalytic A domain is the lethal moiety and contains MONO(ADP-RIBOSE) TRANSFERASES which transfers ADP RIBOSE to PEPTIDE ELONGATION FACTOR 2 thereby inhibiting protein synthesis; and the larger B domain that is needed for entry into cells. Corynebacterium Diphtheriae Toxin,Toxin, Corynebacterium Diphtheriae
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000922 Immunotoxins Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. Affinotoxin,Antibody-Toxin Conjugate,Antibody-Toxin Conjugates,Antibody-Toxin Hybrid,Antibody-Toxin Hybrids,Chimeric Toxins,Cytotoxin-Antibody Conjugate,Cytotoxin-Antibody Conjugates,Monoclonal Antibody-Toxin Conjugate,Targeted Toxin,Targeted Toxins,Toxin Carriers,Toxin Conjugates,Toxin-Antibody Conjugate,Toxin-Antibody Conjugates,Toxin-Antibody Hybrid,Toxin-Antibody Hybrids,Toxins, Chimeric,Toxins, Targeted,Affinotoxins,Chimeric Toxin,Immunotoxin,Monoclonal Antibody-Toxin Conjugates,Toxin Carrier,Toxin Conjugate,Antibody Toxin Conjugate,Antibody Toxin Conjugates,Antibody Toxin Hybrid,Antibody Toxin Hybrids,Antibody-Toxin Conjugate, Monoclonal,Antibody-Toxin Conjugates, Monoclonal,Carrier, Toxin,Carriers, Toxin,Conjugate, Antibody-Toxin,Conjugate, Cytotoxin-Antibody,Conjugate, Monoclonal Antibody-Toxin,Conjugate, Toxin,Conjugate, Toxin-Antibody,Conjugates, Antibody-Toxin,Conjugates, Cytotoxin-Antibody,Conjugates, Monoclonal Antibody-Toxin,Conjugates, Toxin,Conjugates, Toxin-Antibody,Cytotoxin Antibody Conjugate,Cytotoxin Antibody Conjugates,Hybrid, Antibody-Toxin,Hybrid, Toxin-Antibody,Hybrids, Antibody-Toxin,Hybrids, Toxin-Antibody,Monoclonal Antibody Toxin Conjugate,Monoclonal Antibody Toxin Conjugates,Toxin Antibody Conjugate,Toxin Antibody Conjugates,Toxin Antibody Hybrid,Toxin Antibody Hybrids,Toxin, Chimeric,Toxin, Targeted
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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