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CTLs respond with activation and granule secretion when serving target for T cell recognition

Oren Milstein, David Hagin, Assaf Lask, Shlomit Reich-Zeliger, Elias Shezan, Eran Ophir, Yaki Eidelstein, Ran Afik, Yaron E. Antebi, Michael L. Dustin, Yair Reisner
This article has an Erratum 117(20):5551

Abstract

CTLs suppress T cell responses directed against their antigens regardless of their own TCR specificity. This makes the use of CTLs promising for tolerance induction in autoimmunity and transplantation. It has been established that binding of the CTL CD8 molecule to the MHC-I α3 of the recognizing T cell must be allowed for death of the latter to ensue. However, the signaling events that are triggered in the CTL by this molecular interaction in the absence of TCR recognition have never been clarified. Here we employ single cell imaging to study the events occurring in CTLs serving target for recognition by specific T cells. We demonstrate that CTLs actively respond to being recognized by polarizing their cytotoxic granules to the contact area, releasing their lethal cargo and vigorously proliferating. Using CTLs from perforin KO mice and Lck knock-down with specific small interfering RNA, we show that the killing of the recognizing CD8 T cell is perforin dependent and is initiated by Lck signaling in the CTL. Collectively these data suggest a novel mechanism in which the entire cascade generally triggered by TCR engagement is 'hijacked' in CTLs serving target for T cell recognition in the absence of TCR ligation.

  • Submitted May 6, 2010.
  • Accepted September 21, 2010.