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International journal of Immunopathology, allergology, infectology.

Significance of T-cell immunity in multiple myeloma

Mitina T.A., Golenkov A.K., Mitin A.N., Litvina M.M., Donetskova A.D., Nikonova M.F., Komogorova V.V., Sharova N.I., Karaulov A.V.

Moscow regional research clinical institute named after M.F.Vladimirsky, Moscow, Russian Federation
National Research Centre źInstitute of Immunology╗ FMBA of Russia, Moscow, Russian Federation

The process of peripheral T lymphocytes restoration in patients with newly diagnosed multiple myeloma after induction chemotherapy (VCP) was investigated. We have revealed T lymphocytosis in patients with newly diagnosed multiple myeloma, lymphopenia after induction therapy and full restoration of T cells quantity in next 30 days. By means of TREC detection we have determined the reduced contribution of thymus in T-cell immunity restoration owing to thymic hypofunction in these patients. A greater contribution of secondary lymphoid organs in regeneration of peripheral T-lymphatic pool was determined by high percent of proliferating (Ki-67+) T cells. An active immune response as characteristic feature of primary patients with MM was revealed. This was evidenced by increase in the share of proliferating T cells, terminally differentiated effector T lymphocytes, mainly CD8+, and induced regulatory T cells. We have assessed FOXP3 and its isoforms expression by CD4+ T cells from peripheral blood of patients with various forms of multiple myeloma (MM). Significant role of FOXP3 expression by CD4+ T lymphocytes in pathogenesis of MM was shown. Thus, increase of FOXP3-expressing cells percent among CD4+ T cells is registered in patients with newly diagnosed MM and in resistant/relapsed patients. The main contribution to this percent increment is made by FOXP3∆2 isoform expressing cells. In addition to the percent increment the number of CD4+FOXP3+ T cells is also risen in patients with newly diagnosed MM. The level of FOXP3 expression by CD4+ T cells also reflects the effectiveness of antitumor therapy, considering normalization of CD4+FOXP3+ T cells number and percent in patients with disease remission. We also discuss the possible relationship between FOXP3 mRNA post-transcriptional modification, namely alternative splicing, with stable expression of FOXP3 in Tregs.

Keywords

T cells, chemotherapy, lymphopenia, thymopoiesis, multiple myeloma, FOXP3, isoforms, human regulatory T cells

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Mitina T.A., Golenkov A.K., Mitin A.N., Litvina M.M., Donetskova A.D., Nikonova M.F., Komogorova V.V., Sharova N.I., Karaulov A.V. Immunopathology, allergology, infectology 2015; 1:90-104