Cytotoxic T lymphocytes from cathepsin B-deficient mice survive normally in vitro and in vivo after encountering and killing target cells.
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.
Baran
Katherine
K
Cancer Immunology Program, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne 3002, Victoria, Australia.
Ciccone
Annette
A
Peters
Christoph
C
Yagita
Hideo
H
Bird
Phillip I
PI
Villadangos
Jose A
JA
Trapani
Joseph A
JA
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002401:Cathepsin B / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000502:physiology*
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D054353:Perforin; D002401:Cathepsin B