B7-1 synergizes with interleukin-12 in interleukin-2 receptor alpha expression by mouse T helper 1 clones

Eur J Immunol. 1996 Feb;26(2):300-6. doi: 10.1002/eji.1830260205.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antigen-Presenting Cells / immunology
  • B-Lymphocytes / immunology
  • B7-1 Antigen / immunology
  • B7-1 Antigen / pharmacology*
  • Clone Cells
  • Drug Synergism
  • Interleukin-12 / pharmacology*
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / drug effects
  • Receptors, Interleukin-2 / antagonists & inhibitors
  • Receptors, Interleukin-2 / biosynthesis*
  • Receptors, Interleukin-2 / drug effects
  • Tacrolimus / pharmacology
  • Th1 Cells / drug effects*
  • Th1 Cells / metabolism*


  • Antibodies
  • B7-1 Antigen
  • Interleukin-2
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Interleukin-12
  • Tacrolimus