Cost and safety of rush immunotherapy.
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Humans↗
Biomedical subjects
G Gurka
Publications and source records attributed to G Gurka.
Allergen-specific human T cell clones: derivation, specificity, and activation requirements.
The interaction between allergen and immune cells plays a pivotal role in the development of human allergy. In an attempt to understand this interaction, we have studied allergen-specific T cells in vitro. These T cells are derived from rodent-allergic individuals and are specific for a major allergen found in mouse urine (MA-1). Antigen-specific, major histocompatibility complex-restricted, human T cell clones have been generated by limiting dilution from lines derived from the peripheral blood T cells of allergic individuals. Antigen (Ag)-presenting cells are necessary for this response, and they can be modulated by appropriate agents. These clones can be propagated in vitro under conditions of restimulation with Ag in the presence of Ag-presenting cells without the continuous use of exogenous interleukin-2. Most clones are CD3+ or CD4+, but one clone is CD3+ CD8+ by fluorescence-activated cell sorter and monoclonal antibody-killing data. Ag stimulation of these clones induces them to produce interleukin-2 and proliferate. These T cell clones can provide a basis for studying the structure of allergenic epitopes and the potential role of altered Ag in the induction of T cell tolerance. If the determinants of T cell allergen recognition and tolerance are solved, it might provide a basis for a new approach to the immunotherapy of allergic disease.
Antibodies, Monoclonal↗
Biological activity and receptor binding of human prointerleukin-1 beta and subpeptides.
We report here that the human interleukin-1 beta precursor (proIL-1 beta) protein as well as several interleukin-1 beta (IL-1 beta) subpeptides bind cellular receptors specifically and exhibit biological activity by stimulating proliferation of helper T-cells. IL-1 beta polypeptides have been synthesized by in vitro translation of mRNAs transcribed from plasmid vectors containing the bacteriophage SP6 promoter joined to the complete IL-1 beta cDNA or to deletion constructs. The quantity of IL-1 beta in vitro translation products was increased significantly by replacing the cognate IL-1 beta untranslated leader sequence with a 37-nucleotide plant viral untranslated leader. Translation of chimeric mRNAs followed by direct bioactivity assay demonstrated that mature IL-1 beta-(117-269), proIL-1 beta-(1-269), and peptide IL-1-(71-269) were all biologically active. Specific binding to cellular receptors was observed with these three IL-1 beta molecules; moreover, several peptides with minimal biological activity also bound receptor specifically. The biological activity and receptor binding properties of the IL-1 beta proteins reported here contrast with those described by Mosley et al. (Mosley, B., Urdal, D. L., Prickett, K. S., Larsen, A., Cosman, D., Conlon, P. J., Gillis, S., and Dower, S. K. (1987) J. Biol. Chem. 262, 2941-2944; Mosley, B., Dower, S. K., Gillis, S., and Cosman, D. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 4572-4576), who reported that proIL-1 beta-(1-269) had no biological activity and does not bind receptor. Our results indicate that proIL-1 beta is active at a relatively high concentration, and analysis of the proIL-1 beta-(1-269) and IL-1-(71-269) bioactivity data suggests a possible relationship with membrane-bound IL-1.
Chromosome Deletion↗
Immunologic responses during allergen-specific immunotherapy for respiratory allergy.
At present there is no absolute way to determine which patient will respond to immunotherapy and which will not. Even in treated patients who derive clinical benefit, there is no one "best" immunologic parameter to follow although the generation of allergen-specific IgG seems to correlate better with clinical improvement than the other parameters. Whether or not the measurement of allergen-specific IgG4 will prove to be a useful clinical parameter is still a controversial issue and is an area for active investigation. The reason that IgG4 becomes elevated selectively over time during immunotherapy is not clear nor is its function known in the immune response to allergen. It is of interest however that IgG4 does not fix complement and may therefore account for the absence of immune complex disease in patients treated over many years. The modification of allergens through denaturization so that they are less reactive with preformed IgG has resulted in potent preparations that induce a strong IgG response. These preparations permit flexibility in dosage and in frequency of administration as well as produce no greater side effects than aqueous extracts. While these preparations would be a decided advantage over existing extracts, recent information that is accumulating regarding T cell recognition of antigen opens the way for more precise targeting of our therapy. That is, determination of the antigenic epitopes that trigger helper T cells should permit the construction of peptides that can "block" T cell recognition and potentially lead to immunologic unresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
Allergens↗
Reproductive immunology.
The maternal immune system is challenged with paternal antigens through exposure to trophoblast tissue and fetal cells crossing the placenta into the maternal circulation. The dose of antigen, the manner of presentation (cellular, subcellular, or soluble), and the nature of the antigen all determine the type of response that will be elicited. It is also clear that complex maternal immunologic responses, including antibodies to red blood cell antigens, HLA-A, HLA-B, HLA-C, and HLA-D antigens, and cell-mediated responses such as proliferation, lymphokines, cytotoxicity, and suppressor cells, are generated to a variety of paternal antigenic determinants. The fact that some of these reactions are detected in vitro in the absence of maternal serum, but not in its presence, suggests that the local milieu is important in influencing their expression in vivo. For example, such factors as hormones (cortisol, progesterone, and estrogen), pregnancy-associated glycoproteins (alpha 2-macroglobulin and beta 1-glycoprotein) and AFP, which have immunosuppressive properties, may all serve nonspecifically to inhibit and decrease the general tone of maternal immunologic responses, particularly at the placental interface, where many of these factors are present in high concentrations. However, these nonspecific factors may not be sufficient to prevent presensitized effector lymphocytes from continuing an ongoing rejection process, as is often the case in the chronic rejection of an allograft. For this purpose, specific enhancing antibodies would play an important role by blocking maternal responses or protecting the fetus. There may be a subtle balance created on the trophoblast cell surface between specific antibodies and trophoblast or embryonic alloantigens, resulting in limited expression of antigens capable of inducing rejection reactions. This could favor the production of blocking antibodies and/or T-suppressor cells, as opposed to cytotoxic antibody and killer cells. In fact, low levels of antigen density on the cell surface favor a blocking effect by IgG rather than cytotoxicity. Blocking or enhancing antibodies can exert their effect on maternal immunologic responses in several ways. They could block the afferent limb by combining with antigen and preventing sensitization or increasing the level of sensitivity. An example of the latter would be the coating of fetal cells that enter the maternal circulation. Enhancing antibodies could work directly on the effector cells to suppress their function. The antibody itself, or more likely antigen-antibody complexes, may be important in this regard.(ABSTRACT TRUNCATED AT 400 WORDS)
Abortion, Spontaneous↗