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The Journal of Immunology, 1998, 160: 4719-4729.
Copyright © 1998 by The American Association of Immunologists

Direct Evidence That Functionally Impaired CD4+ T Cells Persist In Vivo Following Induction of Peripheral Tolerance1

Kathryn A. Pape, Rebecca Merica, Anna Mondino, Alexander Khoruts and Marc K. Jenkins2

Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455

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-{alpha} 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.




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