PMID- 7636184
OWN - NLM
STAT- MEDLINE
DCOM- 19950912
LR  - 20220419
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 155
IP  - 3
DP  - 1995 Aug 1
TI  - 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.
PG  - 1151-64
AB  - 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.
FAU - Sakaguchi, S
AU  - Sakaguchi S
AD  - Precursory Research for Embryonic Science and Technology (PRESTO), Research and 
      Development Corporation of Japan (JRDC), Tsukuba Life Science Center.
FAU - Sakaguchi, N
AU  - Sakaguchi N
FAU - Asano, M
AU  - Asano M
FAU - Itoh, M
AU  - Itoh M
FAU - Toda, M
AU  - Toda M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Interleukin-2)
RN  - 0 (Isoantigens)
RN  - 0 (Receptors, Interleukin-2)
SB  - IM
CIN - J Immunol. 2011 Apr 1;186(7):3805-7. PMID: 21422250
MH  - Animals
MH  - Autoimmune Diseases/etiology/*immunology/prevention & control
MH  - CD4-Positive T-Lymphocytes/*immunology/metabolism/transplantation
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Female
MH  - Graft vs Host Disease/etiology/*immunology/prevention & control
MH  - Immunotherapy, Adoptive/adverse effects
MH  - Interleukin-2/*physiology
MH  - Isoantigens/immunology
MH  - Lymphocyte Depletion
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Receptors, Interleukin-2/biosynthesis/*physiology
MH  - Self Tolerance/*immunology
MH  - Skin Transplantation/immunology
MH  - T-Lymphocyte Subsets/*immunology/metabolism/transplantation
EDAT- 1995/08/01 00:00
MHDA- 1995/08/01 00:01
CRDT- 1995/08/01 00:00
PHST- 1995/08/01 00:00 [pubmed]
PHST- 1995/08/01 00:01 [medline]
PHST- 1995/08/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1995 Aug 1;155(3):1151-64.