This review considers a crucially new mechanism of T-cell antigen-recognizing repertoire formation. It includes the revision of T-cell antigen receptor (TCR), which implies the secondary rearrangement of TCR genes in peripheral T-lymphocytes and surface expression of a new antigen receptor with altered specificity. Factors and mechanisms involved in the induction of this process have been analyzed. Certain attention is paid to a possible role of TCR revision in the formation of peripheral tolerance in the processes of "avidity maturation" of T-lymphocytes during immune response and also negative consequences related to appearance of potentially autoreactive clones in the periphery.
Melatonin is one of the most multifunctional regulators in the organism. It plays a key role in the control of nerve, endocrine, and immune systems. Due to hormone neuroprotective activity, the possibility is now discussed on its clinical usage in treating neurodegenerative diseases, including multiple sclerosis. At the same time, melatonin is an effective regulator of immune reactions, in part, the reactions toward autoantigens. In this respect, the subset ofT lymphocytes producing IL-17 (Th17) is of special interest. As the Th17 subset plays a key role iri multiple sclerosis pathogenesis, the immunomodulating hormone effects toward Th17, may, in theory, nullify its positive neuroprotective activity.
We studied reactivity of alphabetaT lymphocytes in CBA pregnant females toward male antigens and the presence of gene rearrangement in T-cells antigen receptor in peripheral lymphoid organs of mice in the case of three breeding variants: CBA x BALB/c (normal allogenic pregnancy), CBA x CBA (syngenetic pregnancy), and CBA x DBA/2 (prone to abortion combination). It was shown that proliferative response of alphabetaT lymphocytes in pregnant CBA females to male spleen cells was the most marked at normal allogenic pregnancy, the least marked at syngenic pregnancy, and was not observed at the combination CBA x DBA/2. In addition, cells ofparaaortic lymphatic nodes (draining uterus) respond to male antigen reliably more effectively than lymphocytes in mesenterial and axillary lymphatic nodes. Simultaneous estimation of recombinase RAG-1, the key enzyme in rearrangement of T-receptor genes, revealed similar principles: predominant activity of recombinase in T lymphocytes in paraaortal lymphatic nodes of CBA pregnant females. This points to the relationship between extrathymic rearrangement of antigen receptor genes and change in the antigen-detecting repertoire of these cells. The possible biological significance of the discovered phenomenon is discussed.
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