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, Andrew Mark Pardoll

Research output: Contribution to journalArticle

Abstract

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
Volume164
Issue number2
StatePublished - Jan 15 2000

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Cell Division
T-Lymphocytes
Transgenic Mice
Cell Proliferation

ASJC Scopus subject areas

  • Immunology

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In vivo CD4+ T cell tolerance induction versus priming is independent of the rate and number of cell divisions. / Adler, Adam J.; Huang, Ching Tai; Yochum, Gregory S.; Marsh, David W.; Pardoll, Andrew Mark.

In: Journal of Immunology, Vol. 164, No. 2, 15.01.2000, p. 649-655.

Research output: Contribution to journalArticle

Adler, Adam J. ; Huang, Ching Tai ; Yochum, Gregory S. ; Marsh, David W. ; Pardoll, Andrew Mark. / In vivo CD4+ T cell tolerance induction versus priming is independent of the rate and number of cell divisions. In: Journal of Immunology. 2000 ; Vol. 164, No. 2. pp. 649-655.
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