CD2 regulates T cell-dependent induction of monocyte IL-1 beta mRNA during anti-CD3 mitogenesis.
The induction of monocyte IL-1 mRNA during T cell activation requires that monocytes receive contact-dependent signals from activated T cells. Furthermore, the ability of T cells to induce IL-1 beta mRNA is not constitutive but rather is rapidly acquired (< or = 30 min) following activation via mechanisms that do not require protein synthesis. The goal of these studies is to identify the T cell signal(s) that mediates the cell contact-dependent induction of monocyte IL-1 beta mRNA. The induction of IL-1 beta mRNA during anti-CD3 mitogenesis was significantly inhibited by anti-CD2 mAb, whereas mAb against CD11a, CD18, CD69, or CD5 molecules had no effect. The inhibition of IL-1 beta mRNA induction by anti-CD2 mAb was restricted to only those mAb that block CD2/CD58(LFA-3) interactions. Furthermore, anti-CD2 blocked the induction of monocyte IL-1 beta mRNA by T cells that were preactivated using either immobilized anti-CD3 or anti-T11(2) plus anti-T11(3) mAb, thereby indicating that the inhibition of IL-1 beta mRNA was not due to negative signaling effects exerted on the T cell by anti-CD2. Finally, although anti-CD69 mAb had no effect on IL-1 beta mRNA induction, it inhibited the generation of soluble IL-1 beta. The combination of anti-CD69 and anti-CD2 mAb exhibited greater inhibition of secreted IL-1 beta than either antibody alone. These results indicate that CD2 is required for T cell induction of IL-1 beta mRNA through interaction with LFA-3 on the monocyte and that the generation of soluble IL-1 beta is regulated by CD69.
McAllister
P T
PT
Department of Microbiology and Immunology, Loyola University School of Medicine, Maywood, Illinois 60153, USA.
Ellis
T M
TM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D001667:Binding, Competitive / Q000276:immunology; D018801:CD2 Antigens / Q000276:immunology / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology*; D018968:CD58 Antigens / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008934:Mitogens / Q000276:immunology / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D017252:CD3 Complex; D018968:CD58 Antigens; D007375:Interleukin-1; D008934:Mitogens; D012333:RNA, Messenger