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Publication : Anergy in memory CD4+ T cells is induced by B cells.

First Author  Dalai SK Year  2008
Journal  J Immunol Volume  181
Issue  5 Pages  3221-31
PubMed ID  18713993 Mgi Jnum  J:138953
Mgi Id  MGI:3806903 Doi  10.4049/jimmunol.181.5.3221
Citation  Dalai SK, et al. (2008) Anergy in memory CD4+ T cells is induced by B cells. J Immunol 181(5):3221-31
abstractText  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.
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