Extracellular cystatin F is internalised by cytotoxic T lymphocytes and decreases their cytotoxicityPrunk, Mateja (Avtor) Perišić Nanut, Milica (Avtor) Jakoš, Tanja (Avtor) Sabotič, Jerica (Avtor) Švajger, Urban (Avtor) Kos, Janko (Avtor) cystatin Fcathepsinscytotoxic lymphocytesgranzymesperforinTALL-104Cystatin 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.20202022-02-04 12:59:12Članek v reviji134854UDK: 616.1ISSN pri članku: 2072-6694DOI: 10.3390/cancers12123660COBISS_ID: 43955203sl