Peripheral tolerance to alloantigen results from altered regulation of the interleukin 2 pathway.
Tolerance to alloantigen may be induced in rats by administration of blood followed by transplantation of a renal allograft. The mechanism of this tolerance was investigated by directly analyzing the functional activity of graft-infiltrating cells. We have previously shown cytotoxic T lymphocyte infiltration of, and major histocompatibility complex induction on, grafts of tolerant animals. We now report that cells isolated from the grafts of tolerant rats show a reduced expression of the p55 interleukin 2 receptor (IL-2R) chain on the cell surface compared with that seen on the cells of untreated animals. Scatchard analysis further reveals low expression of high affinity IL-2R. This is due to reduced transcription of both IL-2R alpha and beta chain mRNAs and results in a reduced ability of cells to proliferate in response to IL-2. Cells isolated from tolerant animals are unable to make biologically active IL-2 in culture, whereas cells from untreated animals make high levels. This is not reflected at the mRNA level as the IL-2 gene is induced in both tolerant and untreated animals to similar levels. The induction of tolerance is abrogated by administration of recombinant IL-2 to animals at the time of transplantation. Thus, we conclude that an altered regulation of the IL-2 pathway results in tolerance in these alloantigen-treated and transplanted animals.
Dallman
M J
MJ
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, England.
Shiho
O
O
Page
T H
TH
Wood
K J
KJ
Morris
P J
PJ
D000818:Animals; D007108:Immune Tolerance / Q000502:physiology*; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D007519:Isoantigens / Q000276:immunology*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous / Q000276:immunology
D007376:Interleukin-2; D007519:Isoantigens; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2