INDUCTION OF MHC CLASS-I RESTRICTED HUMAN SUPPRESSOR T-CELLS BY PEPTIDE PRIMING IN-VITRO

The induction of regulatory T cells may offer an effective means for s pecific immunosuppression of autoimmune disease and allograft rejectio n. The existence of suppressor T cells has been previously documented, yet their mechanism of action remains poorly characterized. Our studi es demonstrate that T suppressor (Ts) cell lines can be generated by i n vitro immunization of human PBMCs, with synthetic peptides or solubl e proteins coupled to beads. Such Ts cells express the CD8(+)CD28(-) p henotype and show the following characteristics: (a) antigen specifici ty and restriction by self MHC Class I molecules; (b) limited TCR V be ta gene usage; (c) ability to inhibit antigen-specific, MHC Class II r estricted, Th proliferative responses; and (d) capacity to downregulat e and/or inhibit the upregulation by Th of CD40, CD80, and CD86 molecu les on APCs. The inhibitory activity of Ts on Th proliferation require s the tripartite interaction between Th, Ts, and APCs and results from inefficient costimulation of Th. (C) American Society for Histocompat ibility and Immunogenetics, 1998 published by Elsevier Science Inc.