Resistance of cytotoxic T lymphocytes to the lytic effects of their toxic granules

doi:10.1084/jem.166.5.1536

This Article

	Full Text (PDF, 764K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Verret, C. R.
	Articles by Eisen, H. N.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Verret, C. R.
	Articles by Eisen, H. N.


Social Bookmarking

	What's this?

ARTICLES

Resistance of cytotoxic T lymphocytes to the lytic effects of their toxic granules

CR Verret, AA Firmenich, DM Kranz and HN Eisen
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.

A cytotoxic T lymphocyte (CTL) characteristically kills target cells one after the other by releasing toxic granules that contain one or more cytolytic components. To determine how CTLs avoid destroying themselves when they release granules and lyse target cells, 7 murine CD8+ CTL cell lines were compared with 19 other cell lines for susceptibility to lysis by the isolated toxic granules. Murine CD8+ CTLs were clearly the most resistant cells: granules did not lyse them even after they were exposed to azide, cyanide, and 2-deoxyglucose, conditions that were found to enhance the susceptibility of all the other cells tested, including other T cells. Thus, resistance of CD8+ CTLs to cytotoxic granules appears to be independent of cellular ATP. To reconcile these findings with other observations that, under some circumstances, CTLs can be lysed by other CTLs, we suggest a model in which a CTL releases only a limited proportion of its toxic granules at each antigen-specific encounter with a target cell; the amount released is sufficient to kill most target cells but to leave the CTL undamaged and with enough granules to attack other target cells.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Alves, B., Leong, J., Tamang, D. L., Elliott, V., Lowe, M., Hudig, D. (2009). Hydrolysis of tumor cell lipids after CTL-mediated death. Int Immunol 21: 543-553 [Abstract] [Full Text]
Hallett, W. H.D., Ames, E., Motarjemi, M., Barao, I., Shanker, A., Tamang, D. L., Sayers, T. J., Hudig, D., Murphy, W. J. (2008). Sensitization of Tumor Cells to NK Cell-Mediated Killing by Proteasome Inhibition. J. Immunol. 180: 163-170 [Abstract] [Full Text]
Baran, K., Ciccone, A., Peters, C., Yagita, H., Bird, P. I., Villadangos, J. A., Trapani, J. A. (2006). Cytotoxic T Lymphocytes from Cathepsin B-deficient Mice Survive Normally in Vitro and in Vivo after Encountering and Killing Target Cells. J. Biol. Chem. 281: 30485-30491 [Abstract] [Full Text]
Anikeeva, N., Somersalo, K., Sims, T. N., Thomas, V. K., Dustin, M. L., Sykulev, Y. (2005). Distinct role of lymphocyte function-associated antigen-1 in mediating effective cytolytic activity by cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. USA 102: 6437-6442 [Abstract] [Full Text]
Mekala, D. J., Geiger, T. L. (2003). Functional Segregation of the TCR and Antigen-MHC Complexes on the Surface of CTL. J. Immunol. 171: 4089-4095 [Abstract] [Full Text]
Balaji, K. N., Schaschke, N., Machleidt, W., Catalfamo, M., Henkart, P. A. (2002). Surface Cathepsin B Protects Cytotoxic Lymphocytes from Self-destruction after Degranulation. JEM 196: 493-503 [Abstract] [Full Text]
Lehmann, C., Zeis, M., Schmitz, N., Uharek, L. (2000). Impaired binding of perforin on the surface of tumor cells is a cause of target cell resistance against cytotoxic effector cells. Blood 96: 594-600 [Abstract] [Full Text]
Raftery, M. J., Behrens, C. K., Muller, A., Krammer, P. H., Walczak, H., Schonrich, G. (1999). Herpes Simplex Virus Type 1 Infection of Activated Cytotoxic T Cells: Induction of Fratricide as a Mechanism of Viral Immune Evasion. JEM 190: 1103-1114 [Abstract] [Full Text]
Krenacs, L., Wellmann, A., Sorbara, L., Himmelmann, A. W., Bagdi, E., Jaffe, E. S., Raffeld, M. (1997). Cytotoxic Cell Antigen Expression in Anaplastic Large Cell Lymphomas of T- and Null-Cell Type and Hodgkin's Disease: Evidence for Distinct Cellular Origin. Blood 89: 980-989 [Abstract] [Full Text]