Anergy in memory CD4+ T cells is induced by B cells

Sarat K. Dalai, Saied Mirshahidi, Alexandre Morrot, Fidel Zavala, Scheherazade Sadegh-Nasseri

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3221-3231
Number of pages11
JournalJournal of Immunology
Volume181
Issue number5
DOIs
StatePublished - Sep 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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