Direct evidence that functionally impaired CD4+ T cells persist in vivo following induction of peripheral tolerance

Kathryn A Pape, Rebecca Merica, Anna Mondino, Alexander Khoruts, Marc Jenkins

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160 Scopus citations


A small population of CD4+ OVA-specific TCR transgenic T cells was tracked following the induction of peripheral tolerance by soluble Ag to address whether functionally unresponsive, or anergic T cells, persist in vivo for extended periods of time. Although injection of OVA peptide in the absence of adjuvant caused a transient expansion and deletion of the Ag- specific T cells, a population that showed signs of prior activation persisted in the lymphoid tissues for several months. These surviving OVA- specific T cells had long-lasting, but reversible defects in their ability to proliferate in lymph nodes and secrete IL-2 and TNF-α in vivo following an antigenic challenge. These defects were not associated with the production of Th2-type cytokines or the capacity to suppress the clonal expansion of a bystander population of T cells present in the same lymph nodes. Therefore, our results provide direct evidence that a long-lived population of functionally impaired Ag-specific CD4+ T cells is generated in vivo after exposure to soluble Ag.

Original languageEnglish (US)
Pages (from-to)4719-4729
Number of pages11
JournalJournal of Immunology
Issue number10
StatePublished - May 15 1998


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