Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
J Immunol. 1995 Aug 1;155(3):1151-64. Unique Identifier : AIDSLINE MED/95363080 Sakaguchi S; Sakaguchi N; Asano M; Itoh M; Toda M; Precursory Research for Embryonic Science and Technology; (PRESTO), Research and Development Corporation of Japan (JRDC),; Tsukuba Life Science Center.
Abstract:
Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor alpha-chain (CD25) molecules. When CD4+ cell suspensions prepared from BALB/c nu/+ mice lymph nodes and spleens were depleted of CD25+ cells by specific mAb and C, and then inoculated into BALB/c athymic nude (nu/nu) mice, all recipients spontaneously developed histologically and serologically evident autoimmune diseases (such as thyroiditis, gastritis, insulitis, sialoadenitis, adrenalitis, oophoritis, glomerulonephritis, and polyarthritis); some mice also developed graft-vs-host-like wasting disease. Reconstitution of CD4+CD25+ cells within a limited period after transfer of CD4+CD25- cells prevented these autoimmune developments in a dose-dependent fashion, whereas the reconstitution several days later, or inoculation of an equivalent dose of CD8+ cells, was far less efficient for the prevention. When nu/nu mice were transplanted with allogeneic skins or immunized with xenogeneic proteins at the time of CD25- cell inoculation, they showed significantly heightened immune responses to the skins or proteins, and reconstitution of CD4+CD25+ cells normalized the responses. Taken together, these results indicate that CD4+CD25+ cells contribute to maintaining self-tolerance by down-regulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage; elimination/reduction of CD4+CD25+ cells relieves this general suppression, thereby not only enhancing immune responses to non-self Ags, but also eliciting autoimmune responses to certain self-Ags. Abnormality of this T cell-mediated mechanism of peripheral tolerance can be a possible cause of various autoimmune diseases.
Keywords: Animal Autoimmune Diseases/ETIOLOGY/*IMMUNOLOGY/PREVENTION & CONTROL CD4-Positive T-Lymphocytes/*IMMUNOLOGY/METABOLISM/TRANSPLANTATION CD8-Positive T-Lymphocytes/IMMUNOLOGY Female Graft vs Host Disease/ETIOLOGY/*IMMUNOLOGY/PREVENTION & CONTROL Immunotherapy, Adoptive/ADVERSE EFFECTS Interleukin-2/*PHYSIOLOGY Isoantigens/IMMUNOLOGY Lymphocyte Depletion Mice Mice, Inbred BALB C Mice, Nude Receptors, Interleukin-2/BIOSYNTHESIS/*PHYSIOLOGY Self Tolerance/*IMMUNOLOGY Skin Transplantation/IMMUNOLOGY Support, Non-U.S. Gov't T-Lymphocyte Subsets/*IMMUNOLOGY/METABOLISM/TRANSPLANTATION JOURNAL ARTICLE
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Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
