title: Rat CD8+ FOXP3+ T suppressor cells mediate tolerance to allogeneic heart transplants, inducing PIR-B in APC and rendering the graft invulnerable to rejection.
abstract: Human CD8+ FOXP3+ T suppressor cells (TS) were previously shown to induce the expression of the inhibitory receptors, Immunoglobulin-like transcript (ILT) 3 and ILT4 on dendritic and endothelial cells, rendering them tolerogenic to allogeneic T cells. We have demonstrated the importance of CD8+ TS in a rat model of heart allo-transplantation. Tolerance was induced in ACI recipients by multiple transfusions of UVB-irradiated blood from Lewis heart donors. CD8+ T cells from tolerant ACI rats expressed FOXP3, transferred tolerance to naive secondary hosts and induced the upregulation of the inhibitory receptor, paired immunoglobulin-like receptor (PIR)-B, an ILT4 orthologue, in Lewis dendritic cells (DC) and heart endothelial cells (EC). When long-term surviving Lewis heart allografts with PIR-B+ EC were retransplanted from a primary to a secondary ACI recipient they did not elicit rejection. This study focuses attention on the need to develop agents that act directly on graft EC in order to achieve tolerance.
authors.affiliation: Columbia University, Department of Pathology, 630 West 168th Street-P and S 14-401, New York, NY 10032, USA.
authors.forename: Jiawang
authors.initials: J
authors.lastname: Liu
authors.forename: Zhuoru
authors.initials: Z
authors.lastname: Liu
authors.forename: Piotr
authors.initials: P
authors.lastname: Witkowski
authors.forename: George
authors.initials: G
authors.lastname: Vlad
authors.forename: John S
authors.initials: JS
authors.lastname: Manavalan
authors.forename: Luigi
authors.initials: L
authors.lastname: Scotto
authors.forename: Seunghee
authors.initials: S
authors.lastname: Kim-Schulze
authors.forename: Raffaello
authors.initials: R
authors.lastname: Cortesini
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hardy
authors.forename: Nicole
authors.initials: N
authors.lastname: Suciu-Foca
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology*; D051858:Forkhead Transcription Factors; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism; D016027:Heart Transplantation; D007108:Immune Tolerance / Q000276:immunology; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; C491380:Pirb protein, rat; D011971:Receptors, Immunologic; D014157:Transcription Factors