In vivo CD4+ T cell tolerance induction versus priming is independent of the rate and number of cell divisions

Adam J. Adler, Ching Tai Huang, Gregory S. Yochum, David W. Marsh, Drew M. Pardoll

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73 Scopus citations


In vitro studies have suggested that tolerance induction (i.e., anergy) is associated with an inability of T cells to proliferate vigorously upon Ag recognition. In vivo, the relationship between T cell proliferation and tolerance induction is less clear. To clarify this issue, we have been studying a model system in which naive CD4+ T cells specific for the model Ag hemagluttinin (HA) are adoptively transferred into different transgenic founder lines of mice expressing HA as a peripheral self-Ag. When transferred into two lines whose HA expression differs by at least 1000-fold, HA-specific T cells undergo multiple rounds of cell division before reaching a nonresponsive (i.e., tolerant) state. While the proliferative response is more rapid in mice expressing higher levels of HA, the T cells become tolerant regardless of the level of peripheral HA expression. When the T cells encounter HA expressed as a viral Ag, they proliferate at a similar rate and undergo the same number of divisions as with self-HA, but they do not become tolerant. These results indicate that a tolerizing stimulus can induce similar T cell mitotic rates as a priming stimulus. Therefore, CD4+ T cell tolerance induction in vivo is not the result of an insufficient proliferative response elicited upon TCR engagement.

Original languageEnglish (US)
Pages (from-to)649-655
Number of pages7
JournalJournal of Immunology
Issue number2
StatePublished - Jan 15 2000

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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