CD40 stimulation in vivo does not inhibit CD4+ T cell tolerance to soluble antigens

Jiaren Sun, Nancy Van Houten

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Anergy, or T cell unresponsiveness to antigen, is one mechanism of T cell tolerance. However, the signaling events that lead to immune tolerance are not well understood. A common assumption is that soluble antigens, such as food antigens, are poor immunogens and induce tolerance because they fail to upregulate co-stimulatory molecules on the professional APC. Engagement of CD40 through a stimulatory antibody causes the upregulation of these costimulatory molecules. Using a CD4+ T cell adoptive transfer model specific to ovalbumin (OVA), we show that after upregulation of CD86 on APC through CD40 stimulation in vivo, T cells from OVA-fed mice remain refractory to proliferation, interleukin (IL)-2 and interferon (IFN)-γ production. We conclude that upregulation of CD86 alone does not inhibit oral tolerance induction of CD4+ T cells, indicating that additional signals are involved in the decision process for CD4+ T cells to commit to tolerance versus sensitization. Our data challenge the belief that reconstitution of a costimulatory signal in the presence of soluble antigen is sufficient to override T cell tolerance and anergy.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalImmunology Letters
Issue number2
StatePublished - Nov 1 2002


  • Anergy
  • CD40
  • T lymphocytes
  • Tolerance/suppression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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