Thymic emigration patterns in patients with type 2 diabetes treated with metformin.
Recent data suggest that thymic output, which provides the naive T cells necessary for the normal functioning of T-cell-dependent immunosurveillance cellular immunity including anti-cancer protection, can be disturbed in the course of type 2 diabetes. Metformin, an anti-diabetic drug commonly confirmed as an agent with many potential anti-cancer activities, might be helpful in this immune correction. The profile of thymic output was evaluated in the current study on the basis of the signal-joint T-cell receptor excision circle (sjTREC) concentration in peripheral blood polymorphonuclear cells and thymic emigrant content in peripheral blood evaluated from CD127 and/or CD132 antigen expression. It was revealed that recent thymic emigrants and more differentiated CD127(+) CD132(+) cell populations were decreased among naive T cells and CD8(+) T cells, whereas RTE count was increased in CD4(+) T cells, and the CD127(+) CD132(+) cell population was less numerous than in non-diabetic participants. Terminally differentiated thymic emigrants, i.e. CD127(-) CD132(+) cells, were increased in naive T cells and in CD8(+) T cells. Metformin affects mainly the early phases of thymic export, increasing CD127(+) CD132(-) and CD127(+) CD132(+) cell populations in naive T cells and the CD127(+) CD132(-) population in CD4(+) T lymphocytes. It could be concluded that type 2 diabetes deteriorates thymic immunostasis. The decreased thymic output could be compensated by metformin, especially with regard to CD4(+) naive T cells. It is the first time that therapy with metformin has been documented by us as particularly useful in the control and normalization of thymus function, regarding correction of early populations of thymic emigrants.
Department of Clinical Immunology, Poznan University of Medical Sciences, Poznań, Poland.
Grzegorz
G
Dworacki
Department of Oncology, West Kazakhstan State Medical University, Aktobe, Kazakhstan.
Olzhas
O
Urazayev
Department of Oncology, West Kazakhstan State Medical University, Aktobe, Kazakhstan.
Yerbol
Y
Bekmukhambetov
Department of Pharmacology, West Kazakhstan State Medical University, Aktobe, Kazakhstan.
Saule
S
Iskakova
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznań, Poland.
Bartosz A
BA
Frycz
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznań, Poland.
Paweł P
PP
Jagodziński
Department of Pharmacology, Poznan University of Medical Sciences, Poznań, Poland.
Marzena
M
Dworacka
D000368:Aged; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007156:Immunologic Memory / Q000187:drug effects; D053631:Interleukin Receptor Common gamma Subunit / Q000097:blood; D015851:Interleukin-7 / Q000097:blood; D053699:Interleukin-7 Receptor alpha Subunit / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology
D007004:Hypoglycemic Agents; C507941:IL2RG protein, human; C508605:IL7 protein, human; D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D008687:Metformin
diabetes type 2; metformin; recent thymic emigrants; thymic output