Cell cycle block in anergic T cells during tolerance induction

Jiaren Sun, M. Alison Stalls, Katherine L. Thompson, Nancy Fisher Van Houten

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The induction of anergy, or T cell unresponsiveness to antigen, is preceded by T cell activation and cell division in response to fed antigens. These events parallel the activation observed in T cells following sensitization with antigen and adjuvant. The events that distinguish eventual sensitization versus tolerance remain unclear. Using a T lymphocyte transfer model specific to OVA, we demonstrated previously that oral encounter with antigen leads to functional anergy. Antigen-specific CD4+ T cells nevertheless become activated and cycle briefly after encounter with antigen. In this study, we measured the extent of cell cycling of antigen-specific T cells after oral encounter with their antigen. Whereas T cells cycle on the average of eight times in 4 days after conventional immunization, an abortive proliferation was observed in the draining LN T cells after oral encounter with antigen; OVA-specific T cells divided fewer times after exposure to fed OVA, compared to T cells in mice immunized with OVA. This abortive proliferation is antigen specific and not due to bystander suppression, as coadministration of an unrelated antigen that was previously used as a tolerogen does not alter the degree of abortive proliferation. Measurement of BrdU incorporation in mice that were previously fed ovalbumin indicates that up to 3 days following feeding, OVA-specific cells are actively cycling in vivo. However, by day 4, they have stopped cycling while identical T cells in OVA-sensitized mice continue to cycle. Our results indicate either that tolerance is a default pathway and a secondary stimulus is required at day 3 to progress to sensitization, or that elements that limit cell cycle progression are provided for tolerance induction.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalCellular Immunology
Volume225
Issue number1
DOIs
StatePublished - Sep 2003

Fingerprint

Cell Cycle
T-Lymphocytes
Antigens
Bystander Effect
CD4 Antigens
Ovalbumin
Bromodeoxyuridine
Cell Division
Immunization

Keywords

  • Anergy
  • Cellular proliferation
  • T lymphocytes
  • Tolerance/suppression

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Cell cycle block in anergic T cells during tolerance induction. / Sun, Jiaren; Stalls, M. Alison; Thompson, Katherine L.; Fisher Van Houten, Nancy.

In: Cellular Immunology, Vol. 225, No. 1, 09.2003, p. 33-41.

Research output: Contribution to journalArticle

Sun, J, Stalls, MA, Thompson, KL & Fisher Van Houten, N 2003, 'Cell cycle block in anergic T cells during tolerance induction', Cellular Immunology, vol. 225, no. 1, pp. 33-41. https://doi.org/10.1016/j.cellimm.2003.09.004
Sun, Jiaren ; Stalls, M. Alison ; Thompson, Katherine L. ; Fisher Van Houten, Nancy. / Cell cycle block in anergic T cells during tolerance induction. In: Cellular Immunology. 2003 ; Vol. 225, No. 1. pp. 33-41.
@article{4995712a28b64fb7b19f3dd4f1d29a0c,
title = "Cell cycle block in anergic T cells during tolerance induction",
abstract = "The induction of anergy, or T cell unresponsiveness to antigen, is preceded by T cell activation and cell division in response to fed antigens. These events parallel the activation observed in T cells following sensitization with antigen and adjuvant. The events that distinguish eventual sensitization versus tolerance remain unclear. Using a T lymphocyte transfer model specific to OVA, we demonstrated previously that oral encounter with antigen leads to functional anergy. Antigen-specific CD4+ T cells nevertheless become activated and cycle briefly after encounter with antigen. In this study, we measured the extent of cell cycling of antigen-specific T cells after oral encounter with their antigen. Whereas T cells cycle on the average of eight times in 4 days after conventional immunization, an abortive proliferation was observed in the draining LN T cells after oral encounter with antigen; OVA-specific T cells divided fewer times after exposure to fed OVA, compared to T cells in mice immunized with OVA. This abortive proliferation is antigen specific and not due to bystander suppression, as coadministration of an unrelated antigen that was previously used as a tolerogen does not alter the degree of abortive proliferation. Measurement of BrdU incorporation in mice that were previously fed ovalbumin indicates that up to 3 days following feeding, OVA-specific cells are actively cycling in vivo. However, by day 4, they have stopped cycling while identical T cells in OVA-sensitized mice continue to cycle. Our results indicate either that tolerance is a default pathway and a secondary stimulus is required at day 3 to progress to sensitization, or that elements that limit cell cycle progression are provided for tolerance induction.",
keywords = "Anergy, Cellular proliferation, T lymphocytes, Tolerance/suppression",
author = "Jiaren Sun and Stalls, {M. Alison} and Thompson, {Katherine L.} and {Fisher Van Houten}, Nancy",
year = "2003",
month = "9",
doi = "10.1016/j.cellimm.2003.09.004",
language = "English (US)",
volume = "225",
pages = "33--41",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Cell cycle block in anergic T cells during tolerance induction

AU - Sun, Jiaren

AU - Stalls, M. Alison

AU - Thompson, Katherine L.

AU - Fisher Van Houten, Nancy

PY - 2003/9

Y1 - 2003/9

N2 - The induction of anergy, or T cell unresponsiveness to antigen, is preceded by T cell activation and cell division in response to fed antigens. These events parallel the activation observed in T cells following sensitization with antigen and adjuvant. The events that distinguish eventual sensitization versus tolerance remain unclear. Using a T lymphocyte transfer model specific to OVA, we demonstrated previously that oral encounter with antigen leads to functional anergy. Antigen-specific CD4+ T cells nevertheless become activated and cycle briefly after encounter with antigen. In this study, we measured the extent of cell cycling of antigen-specific T cells after oral encounter with their antigen. Whereas T cells cycle on the average of eight times in 4 days after conventional immunization, an abortive proliferation was observed in the draining LN T cells after oral encounter with antigen; OVA-specific T cells divided fewer times after exposure to fed OVA, compared to T cells in mice immunized with OVA. This abortive proliferation is antigen specific and not due to bystander suppression, as coadministration of an unrelated antigen that was previously used as a tolerogen does not alter the degree of abortive proliferation. Measurement of BrdU incorporation in mice that were previously fed ovalbumin indicates that up to 3 days following feeding, OVA-specific cells are actively cycling in vivo. However, by day 4, they have stopped cycling while identical T cells in OVA-sensitized mice continue to cycle. Our results indicate either that tolerance is a default pathway and a secondary stimulus is required at day 3 to progress to sensitization, or that elements that limit cell cycle progression are provided for tolerance induction.

AB - The induction of anergy, or T cell unresponsiveness to antigen, is preceded by T cell activation and cell division in response to fed antigens. These events parallel the activation observed in T cells following sensitization with antigen and adjuvant. The events that distinguish eventual sensitization versus tolerance remain unclear. Using a T lymphocyte transfer model specific to OVA, we demonstrated previously that oral encounter with antigen leads to functional anergy. Antigen-specific CD4+ T cells nevertheless become activated and cycle briefly after encounter with antigen. In this study, we measured the extent of cell cycling of antigen-specific T cells after oral encounter with their antigen. Whereas T cells cycle on the average of eight times in 4 days after conventional immunization, an abortive proliferation was observed in the draining LN T cells after oral encounter with antigen; OVA-specific T cells divided fewer times after exposure to fed OVA, compared to T cells in mice immunized with OVA. This abortive proliferation is antigen specific and not due to bystander suppression, as coadministration of an unrelated antigen that was previously used as a tolerogen does not alter the degree of abortive proliferation. Measurement of BrdU incorporation in mice that were previously fed ovalbumin indicates that up to 3 days following feeding, OVA-specific cells are actively cycling in vivo. However, by day 4, they have stopped cycling while identical T cells in OVA-sensitized mice continue to cycle. Our results indicate either that tolerance is a default pathway and a secondary stimulus is required at day 3 to progress to sensitization, or that elements that limit cell cycle progression are provided for tolerance induction.

KW - Anergy

KW - Cellular proliferation

KW - T lymphocytes

KW - Tolerance/suppression

UR - http://www.scopus.com/inward/record.url?scp=0344551967&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344551967&partnerID=8YFLogxK

U2 - 10.1016/j.cellimm.2003.09.004

DO - 10.1016/j.cellimm.2003.09.004

M3 - Article

VL - 225

SP - 33

EP - 41

JO - Cellular Immunology

JF - Cellular Immunology

SN - 0008-8749

IS - 1

ER -