Regulatory T Cells Reversibly Suppress Cytotoxic T Cell Function Independent of Effector Differentiation

Thorsten R. Mempel, Mikael J. Pittet, Khashayarsha Khazaie, Wolfgang Weninger, Ralph Weissleder, Harald von Boehmer, Ulrich H. von Andrian

Research output: Contribution to journalArticle

347 Citations (Scopus)

Abstract

Mechanisms of dominant tolerance have evolved within the mammalian immune system to prevent inappropriate immune responses. CD4+CD25+ regulatory T (Treg) cells have emerged as central constituents of this suppressive activity. By using multiphoton intravital microscopy in lymph nodes (LNs) of anesthetized mice, we have analyzed how cytotoxic T lymphocytes (CTLs) interact with antigen-presenting target cells in the presence or absence of activated Treg cells. Nonregulated CTLs killed their targets at a 6.6-fold faster rate than regulated CTLs. In spite of this compromised effector activity, regulated CTLs exhibited no defect in proliferation, induction of cytotoxic effector molecules and secretory granules, in situ motility, or ability to form antigen-dependent conjugates with target cells. Only granule exocytosis by CTLs was markedly impaired in the presence of Treg cells. This selective form of regulation did not require prolonged contact between CTLs and Treg cells but depended on CTL responsiveness to transforming growth factor-β. CTLs quickly regained full killing capacity in LNs upon selective removal of Treg cells. Thus, Treg cells reversibly suppress CTL-mediated immunity by allowing acquisition of full effector potential but withholding the license to kill.

Original languageEnglish (US)
Pages (from-to)129-141
Number of pages13
JournalImmunity
Volume25
Issue number1
DOIs
StatePublished - Jul 2006
Externally publishedYes

Fingerprint

Cytotoxic T-Lymphocytes
Regulatory T-Lymphocytes
T-Lymphocytes
Lymph Nodes
Exocytosis
Secretory Vesicles
Transforming Growth Factors
Antigen-Presenting Cells
Licensure
Immune System
Immunity
Antigens

Keywords

  • CELIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Mempel, T. R., Pittet, M. J., Khazaie, K., Weninger, W., Weissleder, R., von Boehmer, H., & von Andrian, U. H. (2006). Regulatory T Cells Reversibly Suppress Cytotoxic T Cell Function Independent of Effector Differentiation. Immunity, 25(1), 129-141. https://doi.org/10.1016/j.immuni.2006.04.015

Regulatory T Cells Reversibly Suppress Cytotoxic T Cell Function Independent of Effector Differentiation. / Mempel, Thorsten R.; Pittet, Mikael J.; Khazaie, Khashayarsha; Weninger, Wolfgang; Weissleder, Ralph; von Boehmer, Harald; von Andrian, Ulrich H.

In: Immunity, Vol. 25, No. 1, 07.2006, p. 129-141.

Research output: Contribution to journalArticle

Mempel, TR, Pittet, MJ, Khazaie, K, Weninger, W, Weissleder, R, von Boehmer, H & von Andrian, UH 2006, 'Regulatory T Cells Reversibly Suppress Cytotoxic T Cell Function Independent of Effector Differentiation', Immunity, vol. 25, no. 1, pp. 129-141. https://doi.org/10.1016/j.immuni.2006.04.015
Mempel, Thorsten R. ; Pittet, Mikael J. ; Khazaie, Khashayarsha ; Weninger, Wolfgang ; Weissleder, Ralph ; von Boehmer, Harald ; von Andrian, Ulrich H. / Regulatory T Cells Reversibly Suppress Cytotoxic T Cell Function Independent of Effector Differentiation. In: Immunity. 2006 ; Vol. 25, No. 1. pp. 129-141.
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