Avtor/Urednik		Prunk, Mateja; Perišić, Milica; Jakoš, Tanja; Sabotič, Jerica; Švajger, Urban; Kos, Janko
Naslov		Extracellular cystatin F is internalised by cytotoxic T lymphocytes and decreases their cytotoxicity
Tip		članek
Vol. in št.		Letnik 12, št. 12
Leto izdaje		2020
Obseg		str. 1-14
ISSN		2072-6694 - Cancers
Jezik		eng
Abstrakt		Cystatin F is a protein inhibitor of cysteine cathepsins, peptidases involved in the activation of the effector molecules of the perforin/granzyme pathway. Cystatin F was previously shown to regulate natural killer cell cytotoxicity. Here, we show that extracellular cystatin F has a role in regulating the killing efficiency of cytotoxic T lymphocytes (CTLs). Extracellular cystatin F was internalised into TALL-104 cells, a cytotoxic T cell line, and decreased their cathepsin C and H activity. Correspondingly, granzyme A and B activity was also decreased and, most importantly, the killing efficiency of TALL-104 cells as well as primary human CTLs was reduced. The N-terminally truncated form of cystatin F, which can directly inhibit cathepsin C (unlike the full-length form), was more effective than the full-length inhibitor. Furthermore, cystatin F decreased cathepsin L activity, which, however, did not affect perforin processing. Cystatin F derived from K-562 target cells could also decrease the cytotoxicity of TALL-104 cells. These results clearly show that, by inhibiting cysteine cathepsin proteolytic activity, extracellular cystatin F can decrease the cytotoxicity of CTLs and thus compromise their function.
Proste vsebinske oznake		cystatin F cathepsins cytotoxic lymphocytes cistatin F katepsini citotoksični limfociti