TY - JOUR
T1 - Anergy in memory CD4+ T cells is induced by B cells
AU - Dalai, Sarat K.
AU - Mirshahidi, Saied
AU - Morrot, Alexandre
AU - Zavala, Fidel
AU - Sadegh-Nasseri, Scheherazade
PY - 2008/9/1
Y1 - 2008/9/1
N2 - Induction of tolerance in memory T cells has profound implications in the treatment of autoimmune diseases and transplant rejection. Previously, we reported that the presentation of low densities of agonist peptide/MHC class II complexes induced anergy in memory CD4+ T cells. In the present study, we address the specific interaction of different types of APCs with memory CD4+ T cells. A novel ex vivo anergy assay first suggested that B cells induce anergy in memory T cells, and an in vivo cell transfer assay further confirmed those observations. We demonstrated that B cells pulsed with defined doses of Ag anergize memory CD4 cells in vivo. We established that CD11c+ dendritic cells do not contribute to anergy induction to CD4 memory T cells, because diphtheria toxin receptor-transgenic mice that were conditionally depleted of dendritic cells optimally induced anergy in memory CD4+ T cells. Moreover, B cell-deficient muMT mice did not induce anergy in memory T cells. We showed that B2 follicular B cells are the specific subpopulation of B cells that render memory T cells anergic. Furthermore, we present data showing that anergy in this system is mediated by CTLA-4 up-regulation on T cells. This is the first study to demonstrate formally that B cells are the APCs that induce anergy in memory CD4+ T cells.
AB - Induction of tolerance in memory T cells has profound implications in the treatment of autoimmune diseases and transplant rejection. Previously, we reported that the presentation of low densities of agonist peptide/MHC class II complexes induced anergy in memory CD4+ T cells. In the present study, we address the specific interaction of different types of APCs with memory CD4+ T cells. A novel ex vivo anergy assay first suggested that B cells induce anergy in memory T cells, and an in vivo cell transfer assay further confirmed those observations. We demonstrated that B cells pulsed with defined doses of Ag anergize memory CD4 cells in vivo. We established that CD11c+ dendritic cells do not contribute to anergy induction to CD4 memory T cells, because diphtheria toxin receptor-transgenic mice that were conditionally depleted of dendritic cells optimally induced anergy in memory CD4+ T cells. Moreover, B cell-deficient muMT mice did not induce anergy in memory T cells. We showed that B2 follicular B cells are the specific subpopulation of B cells that render memory T cells anergic. Furthermore, we present data showing that anergy in this system is mediated by CTLA-4 up-regulation on T cells. This is the first study to demonstrate formally that B cells are the APCs that induce anergy in memory CD4+ T cells.
UR - http://www.scopus.com/inward/record.url?scp=51549119789&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=51549119789&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.181.5.3221
DO - 10.4049/jimmunol.181.5.3221
M3 - Article
C2 - 18713993
AN - SCOPUS:51549119789
SN - 0022-1767
VL - 181
SP - 3221
EP - 3231
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -