[Dynamics of T-Cell receptor gene rearrangement and T-lymphocytes migration from thymus during post-radiation regeneration].

Recovery and migration of T-cells from the thymus to the secondary lymphoid organs in mice after sublethal gamma irradiation were investigated by measuring T-cell receptor excision circles (TRECs). The TRECs level practically represents the cellularity of thymus, in particular it correlates with the quantity of T-cells which have rearranged TCR genes and express the receptor complex CD3-TCR. So, TRECs can be considered as one of the markers of these cells. TREC-containing cells form a subset of recent thymic emigrants in the secondary lymphoid organs. After a significant TREC decrease in the lymph nodes within the early phase (4 days) after irradiation, we registered the increase of their number during urgent organ recovery due to T-cell migration from the thymus (the maximum is on the 10th day). The secondary thymic atrophy is accompanied by a weakening migration of the T-cells containing TRECs to lymph nodes. A significant TREC increase in the spleen was registered on the 4th day after irradiation. The rest of the recovery period. (up to 60 days) is characterized by the low TREC level. Thus, determination of TREC level allows obtaining additional information about recovery and migratory processes in lymphoid organs during post-radiation regeneration.

[Analysis of cellular bases of secondary thymic atrophy in irradiated mice by flow cytometry].

Using flow cytometry we looked for a thymocyte subpopulation responsible for the development of thymus urgent recovery and secondary atrophy in sublethally irradiated mice (4 Gy). It was expected that the number of these cells would grow before the urgent recovery peak and would drop during secondary atrophy. It was found out that DN3 thymocytes were the best for these criteria. The DN3 stage of thymocytes development is characterized by the rearrangement of the major portion of T-cell receptor genes. On the basis of this finding we have discussed the possibility of secondary atrophy correction using IL-7.

Neolactoferrin as a stimulator of innate and adaptive immunity.

The effect of the innovative product Neolactoferrin, a natural combination of recombinant human lactoferrin (90%) and goat lactoferrin (10%) isolated from the milk of transgenic goats carrying the full-length human lactoferrin gene, on human immune system cells was studied. Neolactoferrin enhanced the production of IL-1ß. Neolactoferrin saturated with iron ions increased the synthesis of pro-inflammatory cytokine TNFα. It determined the direction of the differentiation of precursor dendrite cells. Under the action of T cells, Neolactoferrin amplified the expression of the transcription factors responsible for the differentiation of Th- and Treg-cells and stimulated the production of both IFNγ and IL-4. The results suggest that Neolactoferrin exhibits an immunotropic activity and hinders the development of immune inflammatory processes. Iron saturation of Neolactoferrin increases its pro-inflammatory activity.

Hormone Production by Epithelial Cells of Human Thymus in vitro.

The conditions of hormone production by human thymic stromal cell line were studied. Human thymic stromal cells did not produce any hormones in 5-day monoculture. Co-cultivation of these cells with human thymocytes induced alpha1-thymosin and thymulin production increased to 4-5 days of co-cultivation. An increase in number of human thymic stromal cells and thymocyte elimination were observed in co-culture. The maximal stimulation of proliferation and hormone secretion by human thymic stromal cell was reached in their co-culturing with thymocytes at relative concentrations of 10(4) and 10(7) cells per ml. Thymocyte viability was important for inducing the stimulatory effect. The effect of viable cells could not be replaced by their supernatant. Stimulatory activity of CD4(-)CD8(-) and CD4(+)CD8(+) thymocytes was comparable, alpha1-thymosin and some of its synthetic fragments did not influence alpha1-thymosin synthesis or slightly inhibited it (in high concentrations). Synthetic peptide corresponding to C-terminal half of alpha1-thymosin molecule strongly enhanced production of this hormone.

[Changes in the immune system of the victims of the action of the factors in the accident at the Chernobyl Atomic Electric Power Station. Their manifestations, nature and the possible sequelae]. / Izmeneniia v immunnoi sisteme postradavshikh ot deistviia faktorov avarii na ChAES. Proiavleniia, priroda, vozmozhnye posledstviia.

The hypothesis is formulated, which explains genesis of long-lasting disturbances in the immune system of the persons affected by factors of Chernobyl disaster. Immunological alterations which are displayed at the late time after action of radiation in doses 0.5 Gy or lower are not a result of direct damage of the cells of immune system by irradiation. Their development is more probably a result of appearance of some systemic conditions and factors in affected organism--such as hormonal disbalance and especially autoantibodies of different specificities, including those reactive with thymic epithelial cells. Autoantibodies of the last type induce the decrease of thymic hormone secretion which results in functional deficiency of T lymphocytes. This chain of events is similar to those occurring in aging and does not directly causes development of the clinical displays of immunodeficiency. Only irradiation in doses of 4-6 Gy or higher inducing the structural damage of thymic microenvironment can rouse the long-lasting T cell immunodeficiency with the clinical manifestations.