Inhibitor antibody development and T cell response to human factor VIII in murine hemophilia A.

In order to understand better the mechanism of inhibitor formation in hemophilia A patients, we have characterized the immune response to human factor VIII in a murine model of hemophilia A. Mice with severe factor VIII deficiency caused by targeted gene disruptions in exons 16 and 17 were injected intravenously with human factor VIII. Anti-factor VIII was absent or was detected at only very low levels in hemophilic mice of both strains after a single injection of 0.

[Effect of thymagen, thymalin and vilosen on the cAMP and cGMP levels and phosphodiesterase activity in spleen lymphocytes during sensitization and anaphylactic shock].

It is established that the effect of thymus-derived species is connected with the cyclic nucleotide system. The action of thymus-derived immunocorrectors (thymalin, thymagen, vilosen) on catabolic processes of cyclic nucleotides has been observed under conditions of anaphylaxy and sensibilization. They show that sensibilization of the animal is bound up with a decrease of the cAMP/cGMP ratio.

[Effect of thymic immunomodulators on the system of cyclic nucleotides of splenic T-lymphocytes after BCG vaccination].

The experiments on guinea pigs was performed to study the effects of thymogen , thymalin and vilosene on the activity of cAMP, cGMP, adenylate cyclase, guanylate cyclase, cAMP- and cGMP-phosphodiesterases in T lymphocytes during BCG vaccination. It was shown that the disease was accompanied by increased activity of enzymes of anabolism and catabolism of cyclic nucleotides. Thymogen and thymalin mainly activated the synthesis of cGMP, thus causing the shift of cAMP/cGMP value below the reference level.

[Decrease in adenylate cyclase activity in spleen T- and B-lymphocytes and thymus T-lymphocytes in CBA mice treated with levamisole].

The influence of various concentrations of levamisole on the activity of the membrane adenylate cyclase complex of lymphocytes is analyzed. It is ascertained that levamisole decreases the activity of adenylate cyclase at a concentration of 10(-9)-10(-7) M in thymic lymphocytes, and that the activity of the enzyme in spleen T- and B-lymphocytes remains constant. The influence of levamisole on the activity of adenylate cyclase thymocytes is studied under conditions of its stimulation by NaF, GTF and adrenaline.