Direct evidence that functionally impaired CD4+ T cells persist in vivo following induction of peripheral tolerance.
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.
Pape
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KA
Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA.
Merica
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R
Mondino
A
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Khoruts
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A
Jenkins
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MK
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology
D011948:Receptors, Antigen, T-Cell