Cytotoxic T lymphocytes from cathepsin B-deficient mice survive normally in vitro and in vivo after encountering and killing target cells
- Author(s)
- Baran, K; Ciccone, A; Peters, C; Yagita, H; Bird, PI; Villadangos, JA; Trapani, JA;
- Details
- Publication Year 2006-10-13,Volume 281,Issue #41,Page 30485-30491
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- The lysosomal protease cathepsin B has been proposed to protect cytotoxic T lymphocytes from the membrane-disruptive effects of perforin secreted during the execution phase of target cell death. Accordingly, cathepsin B that translocates to the lymphocyte surface upon degranulation has been postulated to cleave and inactivate perforin molecules that diffuse back to the killer cell. We have found that recombinant perforin is cleaved inefficiently by cathepsin B and shows no significant reduction in its lytic activity following co-incubation. Furthermore, purified CD8+ cytotoxic T lymphocytes of cathepsin B-null gene-targeted mice were able to induce normal death of target cells both in vitro and in vivo and to survive the encounter with target cells as efficiently as cathepsin B-expressing killer cells. We conclude that cathepsin B is not essential for protection of cytotoxic lymphocytes from the toxic effects of their secreted perforin.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- PERFORIN-MEDIATED LYSIS; PORE-FORMING PROTEIN; GRANZYME-B; CYTOLYTIC LYMPHOCYTES; CASPASE ACTIVATION; TOXIC GRANULES; KILLER-CELLS; C2 DOMAIN; BINDING; RESISTANCE
- Publisher's Version
- https://doi.org/10.1074/jbc.M602007200
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-10-13 12:00:00