О неустойчивости решений динамических уравнений на временной шкале

В роботi наведено результати аналiзу нестiйкостi динамiчних рiвнянь на часовiй шкалi. Застосовнiсть отриманого результату iлюструється на прикладi системи другого порядку.We present new results on the instability for dynamic equations on time scales. To demonstrate the applicability, we use some examples of dynamic equations of the second order

A role for CD45RBlow CD38+ T cells and costimulatory pathways of T-cell activation in protection of non-obese diabetic (NOD) mice from diabetes

Non-obese diabetic (NOD) mice spontaneously develop autoimmune insulin-dependent diabetes mellitus (IDDM). Infection of the animals with mycobacteria, or immunization with mycobacteria-containing adjuvant, results in permanent protection of NOD mice from diabetes and we have recently reported that the phenomenon is associated with increased numbers of interferon-γ-producing T cells, possessing increased cytotoxic activity, and also with augmented numbers of activated immunoglobulin M-positive (IgM+) B cells. Here, we have investigated whether protection of NOD mice from IDDM was associated with changes on costimulatory pathways of T and B cells, namely CD28/CTLA-4–B7 and CD40–CD40 ligand (CD40L) and we also further characterized protective T helper (Th) cells with regards to the expression of the differentiation markers CD45RB and CD38. We report that Th cells involved in diabetes vaccination of NOD mice by mycobacterial infection seem to belong to CD45RBlo CD38+ phenotype. The protective effect of Mycobacterium avium infection is also associated with increased CD40L and CTLA-4- expressing Th cells and with the generation of a CD40− IgG+ B cells. Our data are consistent with induction by mycobacterial infection of regulatory CD45RBlo CD38+ Th cells with the ability to trigger deletion or anergy of peripheral self-reactive lymphocytes, with shutting down of IgG+ B-cell response. They also implicate a role for IgG+ B cells in the autoimmune aggression of the endocrine pancreas of NOD mice

The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

CTLA-4, initially described as a membranebound molecule, is a costimulatory receptor transducing a potent inhibitory signal. Increasing evidence shows the CTLA-4 gene to be an important susceptibility locus for autoimmune endocrinopathies and other autoimmune disorders. A soluble form of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) has been established and shown to possess CD80/CD86 binding activity and in vitro immunoregulatory functions. sCTLA-4 is generated by alternatively spliced mRNA. Whereas low levels of sCTLA-4 are detected in normal human serum, increased serum levels are observed in several autoimmune diseases (e.g. Graves’ disease, myasthenia gravis, systemic lupus erythematosus, type 1 diabetes, systemic sclerosis, coeliac disease, autoimmune pancreatitis and primary biliary cirrhosis). The biological significance of increased sCTLA-4 serum levels is not fully clarified yet. On the one hand, it can be envisaged that sCTLA-4 specifically inhibits early T-cell activation by blocking the interaction of CD80/CD86 with the costimulatory receptor CD28. On the other hand, higher levels of sCTLA-4 could compete for the binding of the membrane form of CTLA-4 with CD80/CD86 in the later phases of T-lymphocyte activation, causing a reduction in inhibitory signalling. This double-edged nature of sCTLA-4 to block the binding of CD28 to CD80/CD86 may result in different outcomes during the clinical course of an autoimmune disease