20.500.12556/RUL-135753 Human CD4+ T-cell clone expansion leads to the expression of the cysteine peptidase inhibitor cystatin F The existence of CD4+ cytotoxic T cells (CTLs) at relatively high levels under different pathological conditions in vivo suggests their role in protective and/or pathogenic immune functions. CD4+ CTLs utilize the fundamental cytotoxic effector mechanisms also utilized by CD8+ CTLs and natural killer cells. During long-term cultivation, CD4+ T cells were also shown to acquire cytotoxic functions. In this study, CD4+ human T-cell clones derived from activated peripheral blood lymphocytes of healthy young adults were examined for the expression of cytotoxic machinery components. Cystatin F is a protein inhibitor of cysteine cathepsins, synthesized by CD8+ CTLs and natural killer cells. Cystatin F affects the cytotoxic efficacy of these cells by inhibiting the major progranzyme convertases cathepsins C and H as well as cathepsin L, which is involved in perforin activation. Here, we show that human CD4+ T-cell clones express the cysteine cathepsins that are involved in the activation of granzymes and perforin. CD4+ T-cell clones contained both the inactive, dimeric form as well as the active, monomeric form of cystatin F. As in CD8+ CTLs, cysteine cathepsins C and H were the major targets of cystatin F in CD4+ T-cell clones. Furthermore, CD4+ T-cell clones expressed the active forms of perforin and granzymes A and B. The levels of the cystatin F decreased with time in culture concomitantly with an increase in the activities of granzymes A and B. Therefore, our results suggest that cystatin F plays a role in regulating CD4+ T cell cytotoxicity. Since cystatin F can be secreted and taken up by bystander cells, our results suggest that CD4+ CTLs may also be involved in regulating immune responses through cystatin F secretion. cystatin F CD4+ T helper cells cytotoxic lymphocytes peptidases granzymes true false true Angleški jezik Ni določen Članek v reviji 2022-03-30 13:17:20 2022-03-30 13:17:21 2022-09-14 04:14:59 0000-00-00 00:00:00 2021 0 0 15 str. iss. 16, art. 8408 Vol. 22 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577 1661-6596 10.3390/ijms22168408 72774659 RAZ_Perisic_Milica_2021.pdf RAZ_Perisic_Milica_2021.pdf 1 F1A69EF342B7443273FD797869A930F0 2f9ee755b8015a3c2bdf0aad7106561f6348fc0e2bd69e2c29f7b0c51b6d8556 3b7bcda0-b01b-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=155028 https://www.mdpi.com/1422-0067/22/16/8408 0 095837de-b01b-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=155027 Fakulteta za farmacijo 0 0 0