Incidental CD8 T cell reactivity against caspase-cleaved apoptotic self-antigens from ubiquitously expressed proteins in islets from prediabetic human leucocyte antigen-A2 transgenic non-obese diabetic mice.

Apoptosis is known as a major mechanism which contributes to beta cell decay in type 1 diabetes. Commitment to this pathway generally involves caspase-mediated protein cleavage and was found to induce cross-presentation of a specific antigen repertoire under certain inflammatory conditions. We aimed to assess the significance of the CD8 T cell population reactive against such caspase-cleaved apoptotic self-antigens in pancreatic islets of prediabetic human leucocyte antigen (HLA)-A2 transgenic non-obese diabetic chimeric monochain transgene construct (NOD.HHD) mice. We have reproduced a unique peptide library consisting of human CD8 T cell-derived apoptosis-specific antigens, all of which belong to structural proteins expressed ubiquitously in human islets. Pancreatic islets from prediabetic NOD.HHD mice, harbouring humanized major histocompatibilty complex (MHC) class I, were isolated and handpicked at various ages, and islet-infiltrating CD8 T cells were expanded in vitro and used as responders in an interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay. Human T2 cells were used as antigen-presenting cells (APC) to avoid endogenous antigen presentation. Analogous to the interindividual variability found with peptides from known islet autoantigens such as islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) and insulin, some mice showed variable, low-degree CD8 T cell reactivity against caspase-cleaved self-antigens. Because reactivity was predominantly minor and often undetectable, we conclude that beta cell apoptosis does not routinely provoke the development of dominant cytotoxic T lymphocyte (CTL) reactive against caspase-cleaved self-antigens in the NOD.HHD model.

[Use of sodium nucleinate and its combinations with bacterial polysaccharides for preventing the nephrotoxic action of aminoglycoside antibiotics]. / Primenenie nukelinata natriia i ego sochetanii s bakterial'nymi polisakharidami dlia predotvrashcheniia nefrotoksicheskogo deistviia antibiotikov-aminoglikozidov.

Possible prevention of the nephrotoxic effect of different doses of aminoglycoside antibiotics, such as monomycin, kanamycin and gentamicin was studied experimentally on chinchilla rabbits. Substances increasing the cell resistance (sodium nucleinate, prodigiosan and pyrogenal alone and sodium nucleinate combinations with the bacterial polysaccharides) were used. It was shown that sodium nucleinate prevented nephrotoxicity of the aminoglycosides in the doses 2.5 times higher than the therapeutic ones. The combined use of sodium nucleinate with pyrogenal or prodigiosan was most effective. It prevented the nephrotoxic effect of the antibiotics in the doses 5 times higher than the therapeutic ones.