Proliferation of spleen cells in culture stimulated by 7-thia-8-oxoguanosine: evidence that both B- and T-cells are the targets of its action.
7-thia-8-oxoguanosine (immunosine) is a nucleoside analog showing efficient antiviral activity in rodent models as a consequence of enhancement of the immune response. However, little is known about the mechanisms of its action. In this work the effect of immunosine on proliferation of mouse and rat splenocytes in culture was studied. It was found that the compound stimulated proliferation of lymphocytes in a dose-dependent manner without any additional stimuli. The effect is predominantly mediated by interleukin-2 (IL-2) as judged by increased IL-2 production, upregulation of IL-2 receptor alpha (IL-2R alpha) expression and by significant inhibition (60-75%) of cell proliferation by anti-IL-2R alpha monoclonal antibodies (mAbs). Immunosine also stimulated proliferation both of T- and B-cells purified by immunomagnetic sorting. The response of B-cells was much higher than that of T-cells. The stimulatory effect of immunosine on both lymphocyte subpopulations was further increased by the addition of enriched splenic antigen-presenting cells or purified dendritic cells. Proliferation of purified T-cells to immunosine was also significantly potentiated by an anti-alpha beta T-cell receptor mAb (R 73). All these data suggest that T-, B- and accessory cells in splenic cultures are the targets of immunosine action.
Colic
M
M
Institute of Medical Research, MMA, Belgrade, Yugoslavia.
Vucevic
D
D
Vasilijic
S
S
Popovic
L
L
Pejanovic
V
V
Jandric
D
D
Medic-Mijacevic
L
L
Rakic
L
L
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000502:physiology; D000998:Antiviral Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D051381:Rats; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics; D013154:Spleen / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D006151:Guanosine; C061136:isatoribine