Remote T cell co-stimulation via LFA-1/ICAM-1 and CD2/LFA-3: Demonstration with immobilized ligand/mAb and implication in monocyte-mediated co-stimulation
✍ Scribed by Gijs A. Van Seventer; Yoji Shimizu; Kevin J. Horgan; Gale E. Ginther Luce; Deborah Webb; Stephen Shaw
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- English
- Weight
- 931 KB
- Volume
- 21
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Proliferative response of resting Tcells generally requires not only cross-linking of theTcell receptor (TcR) but also co-stimulatory signals from accessory molecules. We here have used a "three-cell'' model consisting of: (a) resting human CD4+ T cells as responders; (b) CD3 monoclonal antibody (mAb) OKT3 on latex beads as surrogate stimulators; (c) autologous monocytes as source of co-stimulation. As described by Kawakami et al. (1. Zmmunol. 1989.242: 1818),Tcell proliferation in this system is observed with paraformaldehyde-fixed monocytes if they have been activated and interleukin (a) lP/IL 6 is supplied. Since this three-cell system provides TcR cross-linking at a site spatially "remote" from co-stimulation, they help distinguish adhesion from signal transduction but the molecules that mediate co-stimulation in this system have not been identified. Our studies now demonstrate that co-stimulation by the monocytes is dependent on each of two receptornigand pathways CD2LFA-3 and LFA-l/ICAM-1 since it is inhibited by each relevant mAb but not a variety of control mAb. The hypotheses that CD2 and LFA-1 could each mediate co-stimulation was tested in simplified model systems in which the monocyte was replaced with immobilized CD2 mAb or purified ICAM-1 presented on a separate surface from the CD3 mAb.The results in these simplified models demonstrate that on restingTcells either CD2 or LFA-1 molecules alone can mediate "remote" co-stimulation unlike most other T cell surface molecules. Co-stimulation requires IL 1P/IL6 both in the weaker LFA-1 ligand-mediated co-stimulation and at lower CD2 mAb concentrations in the stronger CD2 mAb-mediated co-stimulation.Thus: (a) the accessory cell function of stimulated fixed monocytes in T cell proliferation requires both the LFA-1/ ICAM-1 and CD2LFA-3 pathways; and (b) theTcell molecules CD2 and LFA-1 can give co-stimulatory signals that can act in a "remote" fashion.