Regulatory T Cells Reversibly Suppress Cytotoxic T Cell Function Independent of Effector Differentiation
View/ Open
37866 PIIS1074761306003025.pdf (744.7Kb)
Access Status
Full text of the requested work is not available in DASH at this time ("restricted access"). For more information on restricted deposits, see our FAQ.Author
Mempel, Thorsten R.
Pittet, Mikael J.
Khazaie, Khashayarsha
Weninger, Wolfgang
Weissleder, Ralph
von Boehmer, Harald
von Andrian, Ulrich H.
Published Version
https://doi.org/10.1016/j.immuni.2006.04.015Metadata
Show full item recordCitation
Mempel, Thorsten R., Mikael J. Pittet, Khashayarsha Khazaie, Wolfgang Weninger, Ralph Weissleder, Harald von Boehmer, and Ulrich H. von Andrian. 2006. “Regulatory T Cells Reversibly Suppress Cytotoxic T Cell Function Independent of Effector Differentiation.” Immunity 25 (1): 129–41. https://doi.org/10.1016/j.immuni.2006.04.015.Abstract
Mechanisms of dominant tolerance have evolved within the mammalian immune system to prevent inappropriate immune responses. CD4(+)CD25(+) regulatory T (T-reg) 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 T-reg 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 T-reg cells. This selective form of regulation did not require prolonged contact between CTLs and T-reg cells but depended on CTL responsiveness to transforming growth factor-beta. CTLs quickly regained full killing capacity in LNs upon selective removal of T-reg cells. Thus, T-reg cells reversibly suppress CTL-mediated immunity by allowing acquisition of full effector potential but withholding the license to kill.Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41384213
Collections
- HMS Scholarly Articles [17842]
Contact administrator regarding this item (to report mistakes or request changes)