B7-1 synergizes with interleukin-12 in interleukin-2 receptor alpha expression by mouse T helper 1 clones.
Expression of interleukin-2 receptor alpha (IL-2R alpha) is critical to induce interleukin (IL)-2-dependent proliferation of T helper (Th)1 clones. The IL-2R alpha expression of Th1 clones is known to be up-regulated by IL-12. Co-stimulation via CD28/CTLA-4 is also known to be important for efficient activation of CD4+ T cells. In the present experiments, IL-12-induced enhancement of IL-2R alpha expression of Th1 clones stimulated with B cells as antigen-presenting cells (APC) is suppressed by the addition of anti-B7-1. To analyze the mechanism, Th1 clones were stimulated with immobilized anti-CD3 plus IL-12 in the presence or absence of Chinese hamster ovary cells that express mouse B7-1 (B7-1CHO) and the enhancement of IL-2R alpha expression induced by the co-stimulation was analyzed. The results of these experiments indicate that B7-1 synergizes with IL-12 in IL-2R alpha expression of the Th1 clone stimulated with anti-CD3, although B7-1CHO alone did not enhance IL-2R alpha expression of the clones. B7-1 stimulation is not mediated by the enhancement of IL-2 production: B7-1 enhancement of IL-2R alpha expression was FK506 resistant, while the inclusion of FK506 abrogated IL-2 production of the Th1 cells. B7-1 co-stimulation did not stabilize IL-2E alpha mRNA, but did synergize with IL-12 to enhance IL-2R alpha mRNA transcription.
Igarashi
O
O
Department of Allergology, The Institute of Medical Science, The University of Tokyo, Japan.
Yanagida
T
T
Azuma
M
M
Okumura
K
K
Nariuchi
H
H
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology / Q000494:pharmacology*; D002999:Clone Cells; D004357:Drug Synergism; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism*
D000906:Antibodies; D018122:B7-1 Antigen; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D018664:Interleukin-12; D016559:Tacrolimus