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

Autor: Peter J. Morris, O Shiho, Kathryn J. Wood, Theresa H. Page, Margaret J. Dallman
Rok vydání: 1991
Předmět:
Male
Interleukin 2
Isoantigens
medicine.medical_specialty
II MHC ANTIGENS
T-Lymphocytes
medicine.medical_treatment
Immunology
Research & Experimental Medicine
Major histocompatibility complex
T-CELL TOLERANCE
Polymerase Chain Reaction
Immune tolerance
LYMPHOCYTES-T
Transplantation Immunology
Internal medicine
Immune Tolerance
medicine
Animals
Transplantation
Homologous
Immunology and Allergy
Cytotoxic T cell
RNA
Messenger
Receptor
11 Medical and Health Sciences
TRANSGENIC MICE
Science & Technology
RECEPTOR
biology
INDUCTION
Peripheral tolerance
Receptors
Interleukin-2
Articles
IMMUNOLOGICAL-TOLERANCE
Rats
Transplantation
ACTIVATION PATHWAY
Endocrinology
Cytokine
Medicine
Research & Experimental
Rats
Inbred Lew
biology.protein
Interleukin-2
MESSENGER-RNA
Life Sciences & Biomedicine
TAC ANTIGEN
medicine.drug
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
DOI: 10.1084/jem.173.1.79
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: