Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes
Following proper activation, naïve “CD4lo” T cells differentiate into effector T cells with enhanced expression of CD4 -“CD4hi” effectors. Autoimmune diabetes-prone NOD mice display a unique set of antigen-experienced “CD4lo” T cells that persist after primary stimulation. Here, we report that a p...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2010-01-01
|
Series: | Autoimmune Diseases |
Online Access: | http://dx.doi.org/10.4061/2010/920148 |
id |
doaj-025c118cc8734924a8852829896a9315 |
---|---|
record_format |
Article |
spelling |
doaj-025c118cc8734924a8852829896a93152020-11-25T02:02:58ZengHindawi LimitedAutoimmune Diseases2090-04302010-01-01201010.4061/2010/920148920148Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune DiabetesSean Linkes0Christopher Fry1Anthony Quinn2Department of Biological Sciences, University of Toledo, 2801 W. Bancroft, Toledo, OH 43606, USADepartment of Biological Sciences, University of Toledo, 2801 W. Bancroft, Toledo, OH 43606, USADepartment of Biological Sciences, University of Toledo, 2801 W. Bancroft, Toledo, OH 43606, USAFollowing proper activation, naïve “CD4lo” T cells differentiate into effector T cells with enhanced expression of CD4 -“CD4hi” effectors. Autoimmune diabetes-prone NOD mice display a unique set of antigen-experienced “CD4lo” T cells that persist after primary stimulation. Here, we report that a population of such cells remained after secondary and tertiary TCR stimulation and produced cytokines upon antigenic challenge. However, when NOD blasts were induced in the presence of rIL-15, the number of antigen-experienced “CD4lo” T cells was significantly reduced. Clonal contraction, mediated in part by CD95-dependent activation-induced cell death (AICD), normally regulates the accumulation of “CD4hi” effectors. Interestingly, CD95 expression was dramatically reduced on the AICD-resistant NOD “CD4lo” T cells. Thus, while autoimmune disease has often been attributed to the engagement of robust autoimmunity, we suggest that the inability to effectively contract the immune response distinguishes benign autoimmunity from progressive autoimmune diseases that are characterized by chronic T cell-mediated inflammation.http://dx.doi.org/10.4061/2010/920148 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sean Linkes Christopher Fry Anthony Quinn |
spellingShingle |
Sean Linkes Christopher Fry Anthony Quinn Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes Autoimmune Diseases |
author_facet |
Sean Linkes Christopher Fry Anthony Quinn |
author_sort |
Sean Linkes |
title |
Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes |
title_short |
Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes |
title_full |
Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes |
title_fullStr |
Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes |
title_full_unstemmed |
Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes |
title_sort |
antigen-experienced cd4lo t cells are linked to deficient contraction of the immune response in autoimmune diabetes |
publisher |
Hindawi Limited |
series |
Autoimmune Diseases |
issn |
2090-0430 |
publishDate |
2010-01-01 |
description |
Following proper activation, naïve “CD4lo” T cells differentiate into effector T cells with enhanced expression of CD4 -“CD4hi” effectors. Autoimmune diabetes-prone NOD mice display a unique set of antigen-experienced “CD4lo” T cells that persist after primary stimulation. Here, we report that a population of such cells remained after secondary and tertiary TCR stimulation and produced cytokines upon antigenic challenge. However, when NOD blasts were induced in the presence of rIL-15, the number of antigen-experienced “CD4lo” T cells was significantly reduced. Clonal contraction, mediated in part by CD95-dependent activation-induced cell death (AICD), normally regulates the accumulation of “CD4hi” effectors. Interestingly, CD95 expression was dramatically reduced on the AICD-resistant NOD “CD4lo” T cells. Thus, while autoimmune disease has often been attributed to the engagement of robust autoimmunity, we suggest that the inability to effectively contract the immune response distinguishes benign autoimmunity from progressive autoimmune diseases that are characterized by chronic T cell-mediated inflammation. |
url |
http://dx.doi.org/10.4061/2010/920148 |
work_keys_str_mv |
AT seanlinkes antigenexperiencedcd4lotcellsarelinkedtodeficientcontractionoftheimmuneresponseinautoimmunediabetes AT christopherfry antigenexperiencedcd4lotcellsarelinkedtodeficientcontractionoftheimmuneresponseinautoimmunediabetes AT anthonyquinn antigenexperiencedcd4lotcellsarelinkedtodeficientcontractionoftheimmuneresponseinautoimmunediabetes |
_version_ |
1724950266835369984 |