It has been proposed that the therapeutic effect of PUVA (psoralens+UVA radiation) is connected to its immunomodulative properties, and that the molecular basis of such properties is the oxygen-independent photoaddition of psoralens to DNA. We have investigated effects of preliminary photooxidized psoralens (POP) on the delayed-type hypersensitivity reaction (DTH) to sheep red blood cells and on growth of grafted T-cell lymphoma EL-4 in mice. We have shown that intravenous injection of POP at low concentrations activated, and at high concentrations suppressed, DTH. The POP products are thermolabile. They preserved their immunosuppressive activity for 3 days at room temperature and lost it in several min at 58 degrees C. Incubation of POP in the presence of Fe2+ during 2 h before intravenous injection leads to complete loss of its immunomodulative activity, suggesting a peroxidic nature of POP products. The POP-inhibited growth of grafted T-cell lymphoma independent of the mode of POP application in mice (intravenous or subcutaneous injections, oral or nasal administration). Our data suggest that photooxidative reactions of psoralens, in addition to oxygen-independent photoaddition to DNA, form the basis for biological activity of these drugs.

Functional activity of macrophages and intensity of T cell immune response in mice were studied after intravaginal and intraperitoneal infection with herpes simplex virus type 1 and DNA vaccination in combination with adjuvant treatment (recombinant granulocyte-macrophage colony-stimulating factor and glucosaminylmuramyl dipeptide). DNA vaccination induced a virus-specific T cell immune response with no macrophagic inflammatory reaction. Infection with herpes simplex virus type 1 was accompanied by sustained inflammation, but not by the T cell immune response.

In 3-month bone marrow transplants of CBA mice from bone marrow donors receiving single injections of TLR-4 ligand (LPS) or NOD-2 ligand (muramyl dipeptide, MDP) 24 h before transplantation, an increase in the total number of MSCs (by 2.6 and 1.9 times, respectively), as well as a slight increase in the number of nuclear cells and the mass of bone capsules (by 1.3 and 1.2 times) were observed. After combined administration of MDР and LPS to donors, the total content of MSCs in the grafts was higher by 1.6 times in comparison with the total result of their isolated administration (and by 7.2 times in comparison with the control). At the same time, the concentration of osteogenic MSCs in the grafts of all groups was almost the same and corresponded to the control level. The number of nuclear cells and the mass of bone capsules of the grafts after combined administration of LPS and MDP were close (~80%) to the sum of the results of their isolated administration. These findings suggest that activation of the stromal tissue and the success of bone marrow transplantation depend on the intensity of innate immune responses. These data can be useful for the development of optimal methods of tissue transplantation.

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