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Peripheral tolerance to alloantigen results from altered regulation of the interleukin-2 pathway

Title: Peripheral tolerance to alloantigen results from altered regulation of the interleukin-2 pathway
Authors: DALLMAN, MJ
SHIHO, O
PAGE, TH
WOOD, KJ
MORRIS, PJ
Item Type: Journal Article
Abstract: 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.
Issue Date: 1-Jan-1991
Date of Acceptance: 1-Jan-1991
URI: http://hdl.handle.net/10044/1/72552
DOI: https://dx.doi.org/10.1084/jem.173.1.79
ISSN: 0022-1007
Publisher: Rockefeller University Press
Start Page: 79
End Page: 87
Journal / Book Title: Journal of Experimental Medicine
Volume: 173
Issue: 1
Copyright Statement: © 1991 Rockefeller University Press.
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
T-CELL TOLERANCE
II MHC ANTIGENS
IMMUNOLOGICAL-TOLERANCE
ACTIVATION PATHWAY
TRANSGENIC MICE
LYMPHOCYTES-T
MESSENGER-RNA
TAC ANTIGEN
RECEPTOR
INDUCTION
Animals
Immune Tolerance
Interleukin-2
Isoantigens
Male
Polymerase Chain Reaction
RNA, Messenger
Rats
Rats, Inbred Lew
Receptors, Interleukin-2
T-Lymphocytes
Transplantation Immunology
Transplantation, Homologous
T-Lymphocytes
Animals
Rats, Inbred Lew
Rats
Receptors, Interleukin-2
RNA, Messenger
Interleukin-2
Isoantigens
Transplantation, Homologous
Polymerase Chain Reaction
Immune Tolerance
Transplantation Immunology
Male
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
T-CELL TOLERANCE
II MHC ANTIGENS
IMMUNOLOGICAL-TOLERANCE
ACTIVATION PATHWAY
TRANSGENIC MICE
LYMPHOCYTES-T
MESSENGER-RNA
TAC ANTIGEN
RECEPTOR
INDUCTION
11 Medical and Health Sciences
Immunology
Publication Status: Published
Online Publication Date: 1991-01-01
Appears in Collections:Department of Immunology and Inflammation